Is ABCD1 p.Arg189Trp (c.565C>T) pathogenic?

ABCD1 p.Arg189Trp (c.565C>T) is classified Pathogenic/Likely pathogenic in ABCD1 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2025-12-31). AlphaMissense: likely pathogenic (0.7109); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ABCD1 p.Arg189Trp (c.565C>T)?

ABCD1 p.Arg189Trp (c.565C>T) is associated with Inborn genetic diseases, adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Arg189Trp (c.565C>T) in the general population?

ABCD1 p.Arg189Trp (c.565C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCD1 p.Arg189Trp (c.565C>T)?

AlphaMissense predicts likely pathogenic (score 0.7109) — an in-silico prediction, not a clinical call.

ABCD1 p.Arg189Trp

c.565C>T · rs1131691916 · VCV430349

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

AlphaMissense

likely pathogenic

0.7109 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7109	likely pathogenic ✓ concordant with ClinVar
REVEL	0.969	strongly pathogenic-leaning
SaProt	LLR -16.33	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 1.7	GERP -1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 865 bp · p 0.3 · regional, not allelic
Overall
CADD	26.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCD1
Protein: p.Arg189Trp
Coding: c.565C>T
MANE Select: NM_000033
dbSNP: rs1131691916
Type: single nucleotide variant
Location: chrX:153725831 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 189: a β-strand; a UniProt-annotated variant site (in ald); the abc transmembrane type-1 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.Arg189Gln Conflicting classifications of pathogenicity ★ ⚠ 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-arg189trp (accessed [today's date]).

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