The present study was conducted with the aim to predict the possible associations of Apo E gene SNPs with a deleterious effect on the structural and functional properties of Apo E using different databases such as nucleotide polymorphism database (dbSNP), SIFT, PolyPhen-2 and F-SNP database. The study was performed during 2017–18 using in vitro bioinformatics tools. Bioinformatics tools such as SIFT, PolyPhen-2 and I Mutant 2.0 were used in this study for single amino acid substitution to know tolerance index (TI), protein function and protein stability effects. F-SNP database was used for the identification of disease-causing SNPs. At dbSNP, the data for 333 SNPs were retrieved of Apo E gene. From the study analysis, 333 SNPs were retrieved, of which 63 were nsSNPs and 12 were UTRs and others were located in other regions. From the results, it was inferred that out of 63 nsSNPs, 8 were predicted as ‘Damaging’ with (TI) 0.5. One nsSNP secured the least FS score i.e., rs41382345(0.273). The results in prediction reveals that nsSNPs of Apo E protein have an deleterious impact upon protein function and structure which may lead to serious human health problems. In humans, apolipoprotein E (Apo E) has a vital role in the proper regulation of lipid metabolism. Apo E gene polymorphisms have been associated with coronary heart disease, obesity, diabetes, hypertension, cancers and Alzheimer’ disease. This analysis must be valuable for future genomics, pharmacoproteomics and clinical studies.