ClinVar

Description

This sequence change replaces proline with alanine at codon 86 of the VHL protein (p.Pro86Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of von Hippel-Lindau syndrome (PMID: 17102082, 27034144, 7728151, Invitae). It has also been observed to segregate with disease in related individuals. This variant is also known as c.469C>G in the literature. ClinVar contains an entry for this variant (Variation ID: 93327). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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: 8634692, 9829912, 19464396, 27057652, 27527340, 11257211, 19408298). 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.