ClinVar

Description

This variant has not been reported in the literature in individuals affected with CYP27A1-related conditions. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg479 amino acid residue in CYP27A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 2019602, 21073839, 24584636). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 CYP27A1 protein function. ClinVar contains an entry for this variant (Variation ID: 1479233). This variant is present in population databases (rs199638075, gnomAD 0.008%). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 479 of the CYP27A1 protein (p.Arg479Leu).