ClinVar

Description

An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant is also known as R415C. This missense change has been observed in individual(s) with CYP17A1-related conditions (PMID: 11422109, 16772352, 34724156). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 416 of the CYP17A1 protein (p.Arg416Cys). Experimental studies have shown that this missense change affects CYP17A1 function (PMID: 11422109). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg416 amino acid residue in CYP17A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16849412, 17192295, 28870780). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.