Protein flexibility and conformational changes are known to be key characteristic for the function of many proteins. Factor Xa is a serine protease which activates thrombin and plays a significant role in blood coagulation pathway. Mutations in Factor Xa could be interfaced with thrombosis. To address this issue, we implemented in silico prediction algorithms SIFT, PolyPhen 2.0, I-Mutant 3.0, Align GVGD, to classify the variants as pathogenic. Based on prediction algorithm scores, two variants G406S and G420R were predicted as highly deleterious from a pool of 58 nsSNPs/variants. To analyze the dynamic behavior mutant proteins G406S and G420R, molecular simulation analysis was carried out for 5000ps. This computational work might help us in understanding the effects of mutations on wild Factor Xa protein. © 2015, Scientific Publishers of India. All rights reserved.