ClinVar

Description

This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 19 of the MGP protein (p.Cys19Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant MGP-related spondyloepiphyseal dysplasia (PMID: 37923733). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1373923). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects MGP function (PMID: 37923733). This variant disrupts the p.Cys19 amino acid residue in MGP. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 37923733). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.