Is ABCD1 p.Arg381Phe (c.1141_1142delinsTT) pathogenic?

ABCD1 p.Arg381Phe (c.11411142delinsTT) is classified Uncertain significance in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-23). No gnomAD frequency available for this variant; Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Arg381Phe (c.1141_1142delinsTT)?

ABCD1 p.Arg381Phe (c.1141_1142delinsTT) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Arg381Phe (c.1141_1142delinsTT) in the general population?

ABCD1 p.Arg381Phe (c.1141_1142delinsTT) is no gnomAD frequency available for this variant (gnomAD).

How is X-linked adrenoleukodystrophy inherited?

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

ABCD1 p.Arg381Phe

c.1141_1142delinsTT · rs2522288193 · VCV2850893

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

adrenoleukodystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 14 kb · p 4.8e-06 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABCD1
Protein: p.Arg381Phe
Coding: c.1141_1142delinsTT
MANE Select: NM_000033
dbSNP: rs2522288193
Type: Indel
Location: chrX:153736171 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 381: a β-strand; 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 p.Arg381Cys Uncertain significance ★★ ⚠ same residue
ABCD1 p.Arg381His Likely benign ★ same residue
ABCD1 p.Ala206fs Likely pathogenic ★ same condition
ABCD1 p.Arg6fs Pathogenic ★ same condition
ABCD1 p.Glu292Ile Likely pathogenic ★ same condition
ABCD1 p.Glu302Met Likely pathogenic ★ same condition
ABCD1 p.Met1_Pro2delinsIleSer Pathogenic ★ same condition
ABCD1 p.Pro350fs 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-arg381phe (accessed [today's date]).

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