Miscarriage is the most familiar pregnancy obstacle affecting up to 15% of all clinically recognized pregnancies. Annexin A5 gene is a well-recognized predisposition factor for recurrent spontaneous abortion. Annexin A5 is both Ca2+ and phospholipids binding protein that is localized at the surface of the placental syncytiotrophoblast layer and performs a vital role in anticoagulant function in the maternal blood at the inter villous space. It has been recently shown that polymorphisms in the promoter region of the annexin A5 gene (ANXA5) are significantly associated with RPL. The present study focuses on the comprehensive analysis of the functional and structural impact of all known SNPs of ANXA5 gene by using computational approaches. Comprehensive analysis was performed to filter the most probable mutation that might be associated with RSA. It resulted in identification of SNPs which are most deleterious and disease associated. The study reveals that these two rs111418524, rs41278081 SNPs have more significant effect on structure and function of the protein.