ClinVar

Description

ClinVar contains an entry for this variant (Variation ID: 39260). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg85 amino acid residue in CYP4V2. Other variant(s) that disrupt this residue have been observed in individuals with CYP4V2-related conditions (PMID: 30429639), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This missense change has been observed in individual(s) with Bietti crystalline corneoretinal dystrophy (PMID: 16179904, 30429639; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs199476186, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 85 of the CYP4V2 protein (p.Arg85Cys).