The NM_000033.4:c.1850G>A variant in ABCD1 is a missense variant predicted to cause substitution of arginine by histidine at amino acid 617 (p.Arg617His). At least one patient with this variant displayed elevated VLCFAs and was diagnosed with the childhood cerebral form of adrenoleukodystrophy, which is specific for adrenoleukodystrophy (PP4; PMID 7581394). This variant has been reported in 7 additional probands meeting PP4 phenotype criteria (PS4; PMIDs 8040304, 21068741, 26454440, 20859061, 30902905). This variant has been identified as a de novo occurrence with unconfirmed parental relationships in 1 individual with adrenoleukodystrophy (PS2_Supporting; PMID 8040304). This variant is missing from gnomAD v4.1 genomes (PM2_Supporting). There is a single allele in the exome data but it was flagged by the gnomAD VQSR filter. The computational predictor REVEL gives a score of 0.964, which is above the ClinGen Peroxisomal Disorders VCEP threshold of ≥0.85, evidence that correlates with impact to ABCD1 function (PP3). This variant resides within the Walker B domain (aa 617 – 641), of ABCD1, a critical functional domain as determined by the ClinGen Peroxisomal Disorders VCEP (PM1). Immunofluorescence assay in p.Arg617His variant transfected X-ALD (163) fibroblasts showed a significant reduction of ABCD1 relative to WT control (PS3_Supporting; PMID 17542813). In summary, this variant meets the criteria to be classified as pathogenic for X-linked adrenoleukodystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen Peroxisomal Disorders VCEP: PP4, PS4, PM2_Supporting, PP3, PM1, PS2_Supporting, PS3_Supporting (ClinGen Peroxisomal Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ABCD1 Version 1.0.0)