ClinVar

Description

This variant has been observed in individual(s) with hypophosphatemia (PMID: 26894575, Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 803741). This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with phenylalanine at codon 141 of the PHEX protein (p.Ser141Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. 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. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ser141 amino acid residue in PHEX. Other variant(s) that disrupt this residue have been observed in individuals with PHEX-related conditions (PMID: 10737991), which suggests that this may be a clinically significant amino acid residue.