Factor XI (FXI) deficiency is an autosomal bleeding disorder, usually posttrauma or postsurgery, characterized by reduced levels of coagulation FXI in plasma. The disease is highly prevalent in Ashkenazi Jews (heterozygote frequency, ~9%), whereas it is considered a rare condition in most populations (prevalence of the severe deficiency, 1 in 106 in the white population). So far, >190 causative mutations have been identified throughout the F11 gene. To have a global landscape of genetic variation of F11, we explored publicly available exome-based data obtained from >60 000 individuals belonging to different ethnicities (Exome Aggregation Consortium resource). This analysis revealed profound differences in heterozygote frequencies among populations (allele frequencies: African 5 0.0016; East Asian 5 0.0045; European 5 0.0036; Finnish 5 0.00030; Latino 5 0.0021; South Asian 5 0.0015), and a prevalence significantly higher than that reported so far (eg, the calculated prevalence of the severe deficiency in Europeans would be: 12.9 in 106). In addition, this analysis allowed us to evidence recurrent and ethnic-specific mutations: p.Phe223Leu in Africans (23.5% of all mutated alleles), p.Gln263X and p.Leu424CysfsX in East Asians (28.2% and 20.5%, respectively), and p.Ala412Thr in Latinos (25%).