CP and hemorrhagic disease: To emphasize the significance of these findings, these estimates place ACP in a range of prevalence comparable to that of most rare bleeding disorders.60, 61, 62 Considering the experimentally analysed missense CP variants, these were selected as directly or closely associated with CP residues coordinating Cu2+ or Fe2+ ions (n = 5) and/or those associated with ACP (n = 7, as controls), together with examples of missense variants affecting the signal sequence of CP (n = 4).