ClinVar

Description

This variant has not been reported in the literature in individuals affected with CPA6-related conditions. This variant is present in population databases (rs72654981, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 424 of the CPA6 protein (p.Ala424Val). ClinVar contains an entry for this variant (Variation ID: 472761). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change affects CPA6 function (PMID: 23105115). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CPA6 protein function.