The c.1631A>G (p.Gln544Arg) variant in ABCD1 is a missense variant predicted to cause substitution of glutamine by arginine at amino acid 544 (p.Gln544Arg). At least one patient with this variant displayed rapid progression of inflammatory white matter demyelination in childhood and abnormal very long chain fatty acid testing, which is highly specific for adrenoleukodystrophy (PP4, PMID:10190819). This variant has been reported in 5 additional probands meeting PP4 phenotype criteria (PS4; PMIDs 21068741, 32632637, 10190819, 20661612). This variant is absent from gnomAD v2.1.1, v3.1.2 and v4.1.0 (PM2_Supporting). Beta-oxidation assay in X-ALD fibroblasts (163T) showed that the beta-oxidation activity of the variant protein is approximately 1.6% of wild type ABCD1, indicating that this variant has impact protein function (PMID:17542813)(PS3_Supporting). The computational predictor REVEL gives a score of 0.958, which is above the threshold of 0.85, evidence that correlates with impact to ABCD1 function (PP3). In summary, this variant meets the criteria to be classified as likely pathogenic for X-linked adrenoleukodystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen Peroxisomal Disorders VCEP: PS3_Supporting, PP4, PS4, PM2_Supporting, PP3 (ClinGen Peroxisomal Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ABCD1 Version 1.0.0)