Abstract Background: Epidemiologic data have demonstrated an increased risk of breast cancer development following pregnancy which can last up to 10 years, particularly in women with older age at childbirth. The majority of women with parity associated breast cancer (PABC) undergo genetic testing based on their young age at onset, per current NCCN guidelines. Prior studies have evaluated the interaction of parity and germline BRCA1/2 mutation status, but these have not been extended to other pathogenic germline mutations in known breast cancer susceptibility genes (PALB2, TP53, PTEN, CDH1, CHEK2, ATM, and STK11). Our goal was to evaluate the prevalence of pathogenic germline mutations in a contemporary cohort of women less than 50 diagnosed with breast cancer in relation to their parity status and the time since their most recent pregnancy. Methods: The Northwestern Electronic Database Warehouse was queried for women diagnosed with a new breast cancer between 2010 - 2020 at the age of less than 50 and underwent genetic testing with results available. Patient demographic data, parity history, and genetic testing results were obtained from the structured electronic health records data as well as from semi-structured clinical notes using rule-based text mining methods. 929 women were identified with complete information on parity status, age at first birth, age at most recent birth, breastfeeding status, and germline mutation status. Statistical analyses included Pearson’s chi-square and logistic regression with adjustment for age at diagnosis. Results: 85 women (9.1%) had a germline genetic mutation, with the most prevalent mutations being BRCA1 (3.9%), BRCA2 (2.5%), CHEK2 (0.8%), PALB2 (0.6%) and ATM (0.5%). 90 women (9.7%) had a variant of uncertain significance (VUS) and were included in the no mutation group for analysis. There was no statistically significant difference between nulliparous and parous women in regard to likelihood of having a pathogenic germline genetic mutation (age-adjusted OR 0.85, CI 0.53 -1.29). Among parous women stratified by recency of pregnancy (<5 years, 5-10 years, and >10 years), there was an increased likelihood of having a germline genetic mutation with recency of pregnancy < 5 years (age adjusted OR 2.2, CI 1.07-3.75) compared to women with > 10 years since last pregnancy. Evaluation of each separate germline mutation demonstrated mixed results with CHEK2 mutations more likely with more recent pregnancy (age adjusted OR 3.58, CI 1.13 - 7.57), while PALB2 mutations were less likely with more recent pregnancy (age adjusted OR 0.72, CI 0.52-0.85). The remainder of the mutations were not statistically significantly different among nulliparous vs parous women or when stratified by recency of pregnancy. Conclusions: Nulliparous women with a new diagnosis of breast cancer under the age of 50 were equally as likely to have a germline genetic mutation compared to parous women. After adjusting for age, recency of pregnancy within 5 years of breast cancer diagnosis was associated with increased likelihood of having a germline genetic mutation. The influence of family history of cancer will be addressed in additional analyses. Our data suggest that these mutations may confer an increased risk of parity-associated breast cancer, but need confirmation in larger studies. Citation Format: Erica Wrubel, Saya Rene Dennis, Takahiro Tsukioki, Theresa Sciaraffa, Yuan Luo, Seema A Khan. Frequency of germline mutations in breast cancer susceptibility genes among women under age 50 presenting with parity associated breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-09-15.