Submissions for variant NM_000033.4(ABCD1):c.1529G>A (p.Gly510Asp)

dbSNP: rs2148397558

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002028139	SCV002269893	pathogenic	Adrenoleukodystrophy	2024-09-23	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 510 of the ABCD1 protein (p.Gly510Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with X-linked adrenoleukodystrophy (PMID: 16087056; internal data). ClinVar contains an entry for this variant (Variation ID: 1483831). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ABCD1 protein function with a positive predictive value of 95%. This variant disrupts the p.Gly510 amino acid residue in ABCD1. Other variant(s) that disrupt this residue have been observed in individuals with ABCD1-related conditions (PMID: 22479560), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Johns Hopkins Genomics, Johns Hopkins University	RCV002028139	SCV003839041	likely pathogenic	Adrenoleukodystrophy	2022-10-26	criteria provided, single submitter	clinical testing	This ABCD1 missense variant has been reported in an individual with adolescent cerebral adrenoleukodystrophy. It occurs in the Walker A motif, a region containing multiple missense variants that have been identified in individuals reported with X-linked adrenoleukodystrophy. The variant is absent from a large population dataset but has been reported in ClinVar (Variation ID 1483831). Two bioinformatic tools queried predict that this substitution would be damaging, and the glycine residue at this position is evolutionarily conserved across all of the species assessed. We consider c.1529G>A in ABCD1 to be likely pathogenic.