In the knowledge of the genetic origin of several complicated human disorders, single-nucleotide polymorphisms (SNPs) play a prominent part. Also, understanding the roles of these SNPs may explain the biology of human phenotype heterogeneity. It would still be a big difficulty to describe the gene linked to disease, operational SNPs. We have studied the genetically variation in this study that can affect the expression and functioning of the POLG2 gene by utilizing the in-silico approaches. Among the total of 5828 SNPs, nonsynonymous (ns) SNPs were identified to be 341 and then 3 were recognized as pathogenic. Our analysis was able to classify the future prospects. nsSNPs which can be utilized for certain diseases that occur as just a genetic diagnostic tool. Although, as a disease prediction, the product of abnormality in the POLG2 structure and it is important to experimentally evaluate established nsSNPs. Our outcome showed that 1 nsSNP (rs104894632) exposed to -0.128 kcal/mol found