ClinVar

Description

This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 102 of the PHEX protein (p.Gly102Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hypophosphatemic rickets (Invitae). ClinVar contains an entry for this variant (Variation ID: 1519035). 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.Gly102 amino acid residue in PHEX. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27840894, 30682568; Invitae). 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) performed at Invitae indicates that this missense variant is expected to disrupt PHEX protein function.