ClinVar

Description

The V38G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. However, different amino acid substitutions at this same position (V38M/A) and many missense variants in nearby residues (I33N, M34V/K/T, V35M, L36P, V37L/M, A39P/G/V, A40T/V) have been reported in the Human Gene Mutation Database in association with CMT neuropathy (Stenson et al., 2014), supporting the functional importance of this region of the protein. V38G was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the V38G variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties, and this substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded.