Is ABCD1 p.Ser262Trp (c.785C>G) pathogenic?

ABCD1 p.Ser262Trp (c.785C>G) is classified Pathogenic/Likely pathogenic in ABCD1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-22). AlphaMissense: likely pathogenic (0.9553); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ABCD1 p.Ser262Trp (c.785C>G)?

ABCD1 p.Ser262Trp (c.785C>G) is associated with Inborn genetic diseases, adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Ser262Trp (c.785C>G) in the general population?

ABCD1 p.Ser262Trp (c.785C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCD1 p.Ser262Trp (c.785C>G)?

AlphaMissense predicts likely pathogenic (score 0.9553) — an in-silico prediction, not a clinical call.

ABCD1 p.Ser262Trp

c.785C>G · rs1204814114 · VCV1075691

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9553 · 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	0.9553	likely pathogenic ✓ concordant with ClinVar
REVEL	0.945	strongly pathogenic-leaning
SaProt	LLR -13.39	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 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 865 bp · p 0.3 · regional, not allelic
Overall
CADD	28.3	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.Ser262Trp
Coding: c.785C>G
MANE Select: NM_000033
dbSNP: rs1204814114
Type: single nucleotide variant
Location: chrX:153726051 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 262: a turn; 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.Ser262Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCD1 p.Ser262= Likely benign ★ 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-ser262trp (accessed [today's date]).

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