ClinVar

Description

This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 92 of the SLC45A2 protein (p.Ser92Gly). This variant is present in population databases (rs755311638, gnomAD 0.01%). This missense change has been observed in individual(s) with ocular albinism (PMID: 27734839; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1476655). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SLC45A2 protein function with a positive predictive value of 80%. This variant disrupts the p.Ser92 amino acid residue in SLC45A2. Other variant(s) that disrupt this residue have been observed in individuals with SLC45A2-related conditions (PMID: 34838614), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.