Is ABCD1 p.Arg418Trp (c.1252C>T) pathogenic?

ABCD1 p.Arg418Trp (c.1252C>T) is classified Pathogenic/Likely pathogenic in ABCD1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-12-30). AlphaMissense: likely pathogenic (0.9063); Very rare (popmax 0.00175%, sas); Associated with ABCD1-related disorder.

What condition is associated with ABCD1 p.Arg418Trp (c.1252C>T)?

ABCD1 p.Arg418Trp (c.1252C>T) is associated with ABCD1-related disorder, adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Arg418Trp (c.1252C>T) in the general population?

ABCD1 p.Arg418Trp (c.1252C>T) is very rare (popmax 0.00175%, sas) (gnomAD).

What do computational predictors say about ABCD1 p.Arg418Trp (c.1252C>T)?

AlphaMissense predicts likely pathogenic (score 0.9063) — an in-silico prediction, not a clinical call.

ABCD1 p.Arg418Trp

c.1252C>T · rs128624220 · VCV11301

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely pathogenic

0.9063 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00175%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCD1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9063	likely pathogenic ✓ concordant with ClinVar
REVEL	0.94	strongly pathogenic-leaning
SaProt	LLR -13.73	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 2.5	GERP 0.072, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 14 kb · p 4.8e-06 · regional, not allelic
Overall
CADD	24.2	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

Grpmax group 0.00175% South Asian · 1/57,012 alleles

Overall 9.11e-05% 1/1,098,145 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.Arg418Trp
Coding: c.1252C>T
MANE Select: NM_000033
dbSNP: rs128624220
Type: single nucleotide variant
Location: chrX:153736372 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 418: an α-helix; a UniProt-annotated variant site (in ald; amn-type)

Full ABCD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ABCD1-related disorder

Also linked: adrenoleukodystrophy

Similar variants

ABCD1 p.Arg418Gly Likely pathogenic ★ same residue
ABCD1 p.Arg418Gln 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

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-arg418trp (accessed [today's date]).

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