ClinVar

Description

This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 43 of the ELANE protein (p.Phe43Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with severe congenital neutropenia or cyclic neutropenia (PMID: 14962902, 23463630, 34340247; Invitae). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ELANE protein function. This variant disrupts the p.Phe43 amino acid residue in ELANE. Other variant(s) that disrupt this residue have been observed in individuals with ELANE-related conditions (PMID: 31321910), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.