Is ABCD1 p.Val583Met (c.1747G>A) pathogenic?

ABCD1 p.Val583Met (c.1747G>A) is classified Conflicting classifications of pathogenicity in ABCD1 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-12-29). AlphaMissense: likely pathogenic (0.8857); Ultra-rare (popmax 0.0321%, mid); Associated with ABCD1-related disorder.

What condition is associated with ABCD1 p.Val583Met (c.1747G>A)?

ABCD1 p.Val583Met (c.1747G>A) is associated with ABCD1-related disorder, adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Val583Met (c.1747G>A) in the general population?

ABCD1 p.Val583Met (c.1747G>A) is ultra-rare (popmax 0.0321%, mid) (gnomAD).

What do computational predictors say about ABCD1 p.Val583Met (c.1747G>A)?

AlphaMissense predicts likely pathogenic (score 0.8857) — an in-silico prediction, not a clinical call.

ABCD1 p.Val583Met

c.1747G>A · rs1569541120 · VCV566124

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.8857 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0321%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCD1-related disorder

Computational evidence

Protein change
AlphaMissense	0.8857	likely pathogenic
REVEL	0.866	moderately pathogenic-leaning
SaProt	LLR -13.17	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.38	unconstrained · MANE · 3,261 bp · p 4e-11 · regional, not allelic
Overall
CADD	24.6	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 0.0321% Middle Eastern · 1/3,112 alleles

Overall 0.00266% 3/112,667 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0321%	3,112
Admixed American	0.00218%	45,925
Finnishnot grpmax-eligible	0.00215%	46,579

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.Val583Met
Coding: c.1747G>A
dbSNP: rs1569541120
Type: single nucleotide variant
Location: chrX:153740686 (GRCh38)

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

Disease context

ABCD1-related disorder

Also linked: adrenoleukodystrophy

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-val583met (accessed [today's date]).

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