Is ABCD1 p.Ile481= (c.1443C>T) pathogenic?

ABCD1 p.Ile481= (c.1443C>T) is classified Benign/Likely benign in ABCD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-29). Very rare (popmax 0.00514%, nfe); Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Ile481= (c.1443C>T)?

ABCD1 p.Ile481= (c.1443C>T) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Ile481= (c.1443C>T) in the general population?

ABCD1 p.Ile481= (c.1443C>T) is very rare (popmax 0.00514%, 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.Ile481=

c.1443C>T · rs782704819 · VCV1164548

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00514%, nfe)

Conditions

adrenoleukodystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.122	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -1.2, phastCons 1
Overall
CADD	12.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00514% European (non-Finnish) · 46/895,466 alleles

Filtering AF 0.00394% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00352%

Overall 0.00396% 48/1,210,934 alleles · very rare exomes 47/1,097,571 · genomes 1/113,363 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00514%	19,467
South Asian	0.00176%	56,937
African / African-American	0.00174%	57,627

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.Ile481=
Coding: c.1443C>T
MANE Select: NM_000033
dbSNP: rs782704819
Type: single nucleotide variant
Location: chrX:153737206 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 481: the abc transporter 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.Ile481Val Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCD1 p.Ile481Phe 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-ile481 (accessed [today's date]).

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