Single-nucleotide polymorphisms (SNPs) of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene found in exon 1 are directly associated with the progression and onset of autoimmune disease and various human cancers. These SNPs are commonly known prognostic biomarkers for the prediction and early onset of cancer risk. The variant frequency of CTLA-4 rs231775 (+49 A>G) polymorphisms may affect the various ethnic groups differently. This study assessed the allelic frequency distribution of rs231775 (+49 A>G) polymorphisms in the Saudi Arabian population and compared it with other world populations. The data were extracted from case-control studies in several ethnic groups using PubMed (Medline) and similar web databases. The frequency of CTLA-4 rs231775 (+49 A>G) variant allele (G) was observed at 33.0% and different frequencies were found significant for Pakistan (p=0.02), China (p=0.05), China (p= 0.00), Iran (p=0.00), Poland (p=0.00), the USA (p=0.00) and Turkey (p=0.02) when the prevalence of Saudi Arabian population is compared to that of other populations. The observed finding reveals a distinct pattern of CTLA-4 rs231775 (+49 A>G) polymorphism variant allele in the populations of Saudi Arabia, maybe because of the differences in ethnicity. The observed findings can help assess the risk for the population harboring the risk allele of the rs231775 (+49 A>G) SNP and their subsequent susceptibility to cancer.