Is ABCD1 p.Val201Met (c.601G>A) pathogenic?

ABCD1 p.Val201Met (c.601G>A) is classified Benign/Likely benign in ABCD1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.1416); Rare (popmax 0.163%, afr); Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Val201Met (c.601G>A)?

ABCD1 p.Val201Met (c.601G>A) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Val201Met (c.601G>A) in the general population?

ABCD1 p.Val201Met (c.601G>A) is rare (popmax 0.163%, afr) (gnomAD).

How is X-linked adrenoleukodystrophy inherited?

Typically X-linked dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ABCD1 p.Val201Met (c.601G>A)?

AlphaMissense predicts likely benign (score 0.1416) — an in-silico prediction, not a clinical call.

ABCD1 p.Val201Met

c.601G>A · rs139415350 · VCV585357

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1416 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.163%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

adrenoleukodystrophy

ClinGen expert panel — Peroxisomal Disorders VCEP

Benign for adrenoleukodystrophy. Applied ACMG criteria (verbatim):

BP4 BA1

Curation rationale (ClinGen, verbatim)

The c.601G>A (NM_000033.4) variant in ABCD1 is a missense variant predicted to cause substitution of Valine by Methionine at amino acid 201 (p.Val201Met). The GrpMax filtering allele frequency is 0.001360, gnomAD v4.1, which is higher than the ClinGen Peroxisomal Disorders VCEP threshold of ≥0.00017 for BA1, and therefore meets this criterion (BA1). The computational predictor REVEL gives a score of 0.423, (threshold ≤0.5) and the splice site predictor SpliceAI indicated that the variant has no impact on splicing with a score of 0.00 for donor/acceptor and loss/gain (threshold ≤0.1), evidence that does not predict a damaging effect on ABCD1 function (BP4). In summary, this variant meets the criteria to be classified as Benign for X-linked adrenoleukodystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen Peroxisomal VCEP: BA1, BP4. (ClinGen Peroxisomal Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ABCD1 Version 1.0.0)

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

Computational evidence

Protein change
AlphaMissense	0.1416	likely benign
REVEL	0.423	indeterminate
SaProt	LLR -9.90	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -1.9, phastCons 0.93
Regional constraint	o/e 0.94	unconstrained · MANE · 865 bp · p 0.3 · regional, not allelic
Overall
CADD	17.96	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.163% African / African-American · 94/57,790 alleles

Filtering AF 0.136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.126%

Overall 0.0108% 131/1,210,757 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.163%	615
Remaining individualsnot grpmax-eligible	0.0315%	3,176
Admixed American	0.0239%	4,189
European (non-Finnish)	0.00123%	81,410

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABCD1
Protein: p.Val201Met
Coding: c.601G>A
MANE Select: NM_000033
dbSNP: rs139415350
Type: single nucleotide variant
Location: chrX:153725867 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 201: an α-helix; the abc transmembrane type-1 domain

Full ABCD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

adrenoleukodystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked adrenoleukodystrophy (Orphanet):

Inheritance: X-linked dominant
Onset: Adolescent, Adult, Childhood, Elderly
Prevalence: 1-9 / 1 000 000 (Israel)

Similar variants

ABCD1 p.Val201= Likely benign ★ same residue
ABCD1 p.Val201_Ala206del Uncertain significance ★ same residue
ABCD1 c.1635-2A>G Pathogenic ★★ same condition
ABCD1 c.1781-1G>C Pathogenic ★★ same condition
ABCD1 c.1781-1G>T Pathogenic/Likely pathogenic ★★ same condition
ABCD1 c.1866-10G>A Pathogenic/Likely pathogenic ★★ same condition
ABCD1 c.1866-1G>C Likely pathogenic ★★ same condition
ABCD1 c.1866-2A>T Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abcd1-p-val201met (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown