ClinVar

Description

This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 86 of the VHL protein (p.Pro86Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with von Hippel-Lindau syndrome (PMID: 9829911, 11257211, 17024664, 19408298). ClinVar contains an entry for this variant (Variation ID: 223170). 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 VHL protein function. This variant disrupts the p.Pro86 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9829912, 10205047, 22799452, 27034144, 27057652, 27527340). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.