ClinVar

Description

The P714L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. 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. The P714L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position in a B30.2/SPRY domain that is not conserved across species, and in silico analysis predicts this variant likely does not alter the protein structure/function. However, missense pathogenic variants in nearby residues (K716M and R717S/L/H) have been reported in the Human Gene Mutation Database in association with familial Mediterranean fever and PFAPA syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.