Is ABCD1 p.Asn509Ser (c.1526A>G) pathogenic?

ABCD1 p.Asn509Ser (c.1526A>G) is classified Conflicting classifications of pathogenicity in ABCD1 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-11-27). AlphaMissense: likely pathogenic (0.5709); Very rare (popmax 0.00348%, afr); Associated with Inborn genetic diseases.

What condition is associated with ABCD1 p.Asn509Ser (c.1526A>G)?

ABCD1 p.Asn509Ser (c.1526A>G) is associated with Inborn genetic diseases, adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Asn509Ser (c.1526A>G) in the general population?

ABCD1 p.Asn509Ser (c.1526A>G) is very rare (popmax 0.00348%, afr) (gnomAD).

What do computational predictors say about ABCD1 p.Asn509Ser (c.1526A>G)?

AlphaMissense predicts likely pathogenic (score 0.5709) — an in-silico prediction, not a clinical call.

ABCD1 p.Asn509Ser

c.1526A>G · rs782158792 · VCV458633

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.5709 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00348%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5709	likely pathogenic
REVEL	0.791	moderately pathogenic-leaning
SaProt	LLR -11.03	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 14 kb · p 4.8e-06 · regional, not allelic
Overall
CADD	23.8	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 0.00348% African / African-American · 2/57,443 alleles

Filtering AF 0.000577% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000216%

Overall 0.000661% 8/1,209,600 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00348%	28,722
Admixed American	0.00218%	45,888
European (non-Finnish)	0.000559%	178,893

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.Asn509Ser
Coding: c.1526A>G
MANE Select: NM_000033
dbSNP: rs782158792
Type: single nucleotide variant
Location: chrX:153740129 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 509: a binding site; the abc transporter domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: adrenoleukodystrophy

Similar variants

ABCD1 p.Asn509Lys 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
ABCD1 c.901-1G>A 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-asn509ser (accessed [today's date]).

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