The Factor V Leiden mutation is the most common inherited thrombophilia because it leads to resistance to activated protein C, resulting in a hypercoagulable state. This mutation increases the risk of venous thromboembolism significantly more than other inherited deficiencies. Unlike Protein C or Antithrombin III deficiencies, Factor V Leiden is found in 3-8% of the Caucasian population, making it the most prevalent genetic risk factor for thrombosis. Identification of this mutation is crucial for managing patients with unexplained thrombosis or family history of clotting disorders.

Reference: Harrison's Principles of Internal Medicine, 20th Edition.