With the recent explosion in high-throughput genotyping tech-nology, the amount and quality of SNP data have increased expo-nentially, facilitating the discovery of multiple uncommon SNPs in the human population. To provide unified and centralized resources for the scientific community, several repositories have been devel-oped that aggregate numerous population studies and serve widely as references to filter natural variants in genetic analyses. However, they are largely biased toward European populations. TP53 gene is the most frequently mutated gene in human cancer, and pathogenic germline TP53 variants are associated with several cancer suscep-tibility disorders such as Li-Fraumeni syndrome. For these reasons, it is essential that TP53 SNPs are rigorously evaluated to avoid misclassifications that could impair patient management. The recent discovery of numerous benign SNPs within the coding region of TP53 can be attributed to surveillance of both global repositories and population-specific databases, with the latter enabling the recognition of additional TP53 SNPs in Japanese, African, and Indian populations. This review summarizes the body of evidence behind the identification of 21 TP53 variants and the information defining them as bona fide SNPs. This illustrates the need to include populations of different ethnic origins in genetic studies and the substantial benefits that can be derived from the information.