ClinVar

Description

The P11L variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It 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 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 within the ribosomal protein S5 domain 2-type fold that is conserved across species. This variant is not predicted to affect splicing and in-silico analysis predicts this variant is probably damaging to the protein structure/function. Missense mutations in nearby residues (A10V and G12R) have been reported in the Human Gene Mutation Database in association with hyperimmunoglobulin D and periodic fevers (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 mutation or a rare benign variant.