In this article, we present a speculative analysis of two aspects of the FOP pathogenesis related to the ACVR1 mutation itself: (a) why a single mutation has such a high prevalence in FOP patients; and (b) how the expression of ACVR1 can be modulated by cis-acting variants in the surrounding genomic region of the gene in human chromosome 2q, thus affecting FOP expressivity. This evidence concerns the gene ACVR1 and fibrodysplasia ossificans progressiva.