Is ABCD1 p.Glu439= (c.1317G>A) pathogenic?

ABCD1 p.Glu439= (c.1317G>A) is classified Likely benign in ABCD1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-02). Ultra-rare (popmax 0.0191%, afr); Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Glu439= (c.1317G>A)?

ABCD1 p.Glu439= (c.1317G>A) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Glu439= (c.1317G>A) in the general population?

ABCD1 p.Glu439= (c.1317G>A) is ultra-rare (popmax 0.0191%, afr) (gnomAD).

How is X-linked adrenoleukodystrophy inherited?

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

ABCD1 p.Glu439=

c.1317G>A · rs200522486 · VCV1115181

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0191%, afr)

Conditions

adrenoleukodystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.021	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -1.3, phastCons 0.99
Overall
CADD	3.098	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0191% African / African-American · 11/57,452 alleles

Filtering AF 0.0107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00827%

Overall 0.00198% 24/1,210,780 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0273%	3,664
African / African-Americangrpmax	0.0191%	5,223

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu439=
Coding: c.1317G>A
MANE Select: NM_000033
dbSNP: rs200522486
Type: single nucleotide variant
Location: chrX:153736437 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB

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 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
ABCD1 c.901-5C>A 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-glu439 (accessed [today's date]).

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