ClinVar

Description

The G48D variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge; however, this variant was observed apparently de novo in a patient referred for RASopathy spectrum disorders in our laboratory. The variant 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. G48D is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.