Is ABCD1 p.Val347fs (c.1039del) pathogenic?

ABCD1 p.Val347fs (c.1039del) is classified Likely pathogenic in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-12). Very rare (popmax 0.000112%, nfe); Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Val347fs (c.1039del)?

ABCD1 p.Val347fs (c.1039del) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Val347fs (c.1039del) in the general population?

ABCD1 p.Val347fs (c.1039del) is very rare (popmax 0.000112%, nfe) (gnomAD).

How is X-linked adrenoleukodystrophy inherited?

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

ABCD1 p.Val347fs

c.1039del · VCV4795941

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Conditions

adrenoleukodystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/895,365 alleles

Overall 9.11e-05% 1/1,097,958 alleles · very rare

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.Val347fs
Coding: c.1039del
MANE Select: NM_000033
Type: Deletion
Location: chrX:153729369 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 347: 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 c.1394-2_1404del Pathogenic/Likely pathogenic ★★ same condition
ABCD1 c.901-48_909del Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Ala241fs Pathogenic ★★ same condition
ABCD1 p.Arg80_Leu82del Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Gln472fs Pathogenic ★★ same condition
ABCD1 p.Gln645fs Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Glu371fs Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Glu477fs 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-val347fs (accessed [today's date]).

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