<h3>Objective:</h3> Assess the prevalence of pathogenic variants among people with Parkinson’s disease (PWP) through the PD GENEration study’s 7-gene genetic testing panel (<i>LRRK2, GBA, SNCA, PRKN, PINK1, PARK7 and VPS35</i>) and determine predictors of pathogenic variants. <h3>Background:</h3> While precision medicine trials for PD have started, widespread access to clinical genetic testing and counseling for a large North American PD cohort has been limited. <h3>Design/Methods:</h3> This multi-center observational study provides genetic counseling and CLIA-certified genetic testing for PWP in the U.S., Canada and the Dominican Republic. DNA samples (buccal swab or blood) undergo next generation sequencing including deletion/duplication analyses. Pathogenic (P), likely pathogenic (LP) and select risk allele (RA) variants based on the American College of Medical Genetics (ACMG) classification criteria are returned to participants. <h3>Results:</h3> Over 5,500 participants have enrolled in the study between September 5, 2019 and October 1, 2022. Of the 4,080 completed tests, 563 individuals (13.8%) carried a reportable variant (P, LP, RA). The distribution of positive cases include: 338 <i>GBA</i>, 106 <i>LRRK2</i>, 94 <i>PRKN</i>, 6 <i>VPS35</i>, 9 <i>SNCA</i>, 5 <i>PINK1</i>, 5 <i>PARK7</i>, including 22 (0.54%) participants carrying variants in more than one gene. 1,860 out of 4,080 participants were viewed as having a higher genetic risk due to ancestry, positive first-degree family history, or age of onset <50; of those, 385, or 20.7%, were found to have a disease-related genetic variant. Of the other 2,220 participants with none of the above risk factors, 178, or 8.0%, had an abnormal genetic result. <h3>Conclusions:</h3> Genetic testing of well-established PD genes in this North American cohort resulted in a genetic diagnostic yield of 13.8%. Although reportable variants were more likely to be found in individuals who had early-onset PD, high-risk ancestry or a positive family history, a yield of approximately 8.0% was observed in those without these features. <b>Disclosure:</b> Dr. Beck has received personal compensation for serving as an employee of Parkinson. Kamalini Ghosh Galvelis has nothing to disclose. Dr. Nance has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Voyager. Dr. Nance has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ROche. Dr. Nance has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Nance has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Uniqure. An immediate family member of Dr. Nance has received stock or an ownership interest from Fresca. The institution of Dr. Nance has received research support from HDSA. The institution of Dr. Nance has received research support from Parkinson Foundation. Dr. Nance has received research support from Parkinson Foundation. The institution of Dr. Nance has received research support from Neuraly. Dr. Nance has received personal compensation in the range of $500-$4,999 for serving as a speaker with AAN. Anna Naito has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Parkinson’s Foundation. The institution of Dr. Mencacci has received research support from Parkinson’s foundation. Ignacio Mata has nothing to disclose. Anne Hall has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Parkinson’s Foundation . Anne Hall has received personal compensation in the range of $500-$4,999 for serving as a Patient Engagement Collaborative, member with Duke University . Jeanine Schulze has nothing to disclose. Mrs. Delgado Hodges has received personal compensation in the range of $0-$499 for serving as a PD GENEration Latino Advisory Committee with Parkinson’s Foundation. Dr. Wills has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Accordant, a CVS/Caremark company. Dr. Wills has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi/Genzyme. The institution of Dr. Wills has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono Pharmaceuticals. The institution of Dr. Wills has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx. Dr. Wills has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Parkinson’s Foundation. The institution of Dr. Wills has received research support from Parkinson’s Foundation. The institution of Dr. Wills has received research support from Biogen. The institution of Dr. Wills has received research support from Roche/Genentech. The institution of Dr. Wills has received research support from BioSensics. The institution of Dr. Schwarzschild has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bial Biotech (indirectly, as a service of the Parkinson Study Group service). The institution of Dr. Schwarzschild has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen (indirectly, as a service of the Parkinson Study Group service). The institution of Dr. Schwarzschild has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB (indirectly, as a service of the Parkinson Study Group service). Dr. Schwarzschild has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. The institution of Dr. Schwarzschild has received research support from NIH. The institution of Dr. Schwarzschild has received research support from Parkinson’s Foundation. The institution of Dr. Schwarzschild has received research support from Michael J Fox Foundation. The institution of Dr. Schwarzschild has received research support from Farmer Family Foundation. Dr. Schwarzschild has a non-compensated relationship as a Chair, Executive Committee with the Parkinson Study Group that is relevant to AAN interests or activities. Dr. Marder has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Marder has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Marder has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Parkinson’s Foundation . Dr. Marder has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CHDI. Dr. Marder has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC therapeutics. Dr. Marder has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer LTD. The institution of Dr. Marder has received research support from Vaccinex. The institution of Dr. Marder has received research support from Genentech. The institution of Dr. Marder has received research support from Triplet Therapeutics. The institution of Dr. Marder has received research support from Prilenia. Dr. Simuni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acadia, Abbvie, Accorda, Adamas, Allergan, Amneal, Aptinyx, Denali, General Electric (GE), Kyowa, Neuroderm, Neurocrine, Sanofi, Sinopia, Sunovion, Roche, Takeda, Voyager, US World Meds, Parkinson’s Foundation, and the Michael J. Fox Foundation for Parkinson’s Research. Dr. Simuni has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neuroderm and Sanofi. Dr. Simuni has received research support from NINDS, Parkinson’s Foundation, MJFF, Biogen, Roche, Neuroderm, Sanofi, Sun Pharma, Abbvie, IMPAX and Prevail. . Mrs. MILLER has nothing to disclose. Jennifer Verbrugge has nothing to disclose. Lola Shukla has nothing to disclose. Mrs. Heathers has nothing to disclose. Mrs. Totten has nothing to disclose. The institution of Dr. Foroud has received research support from NIH. The institution of Dr. Foroud has received research support from Michael J. Fox Foundation. The institution of Dr. Foroud has received research support from Parkinson Foundation. Dr. Foroud has received personal compensation in the range of $500-$4,999 for serving as a Member of an Advisory Committee with Mayo Clinic, University of Pennsylvania, . Dr. Alcalay has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genzyme/Sanofi. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono Therapeutics. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Caraway. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avrobio. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. The institution of Dr. Alcalay has received research support from NIH. The institution of Dr. Alcalay has received research support from DoD. The institution of Dr. Alcalay has received research support from Michael J. Fox Foundation. Dr. Alcalay has received research support from Parkinson’s Foundation.