Is ABCD1 p.Arg660Trp (c.1978C>T) pathogenic?

ABCD1 p.Arg660Trp (c.1978C>T) is classified Pathogenic in ABCD1 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-06-06). AlphaMissense: likely pathogenic (0.9785); Absent from gnomAD v4.1; Associated with ABCD1-related disorder.

What condition is associated with ABCD1 p.Arg660Trp (c.1978C>T)?

ABCD1 p.Arg660Trp (c.1978C>T) is associated with ABCD1-related disorder, adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Arg660Trp (c.1978C>T) in the general population?

ABCD1 p.Arg660Trp (c.1978C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCD1 p.Arg660Trp (c.1978C>T)?

AlphaMissense predicts likely pathogenic (score 0.9785) — an in-silico prediction, not a clinical call.

ABCD1 p.Arg660Trp

c.1978C>T · rs1569541203 · VCV585302

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

AlphaMissense

likely pathogenic

0.9785 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCD1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9785	likely pathogenic ✓ concordant with ClinVar · top 10% in ABCD1
REVEL	0.936	strongly pathogenic-leaning
SaProt	LLR -15.78	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 3.2	GERP -1.2, phastCons 1
Regional constraint	o/e 0.38	unconstrained · MANE · 3,261 bp · p 4e-11 · regional, not allelic
Overall
CADD	27.6	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.Arg660Trp
Coding: c.1978C>T
MANE Select: NM_000033
dbSNP: rs1569541203
Type: single nucleotide variant
Location: chrX:153743333 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 660: the 'required for homodimerization' region; a UniProt-annotated variant site (in ald; cald-type); a UniProt-annotated variant site (in ald); a UniProt-annotated variant site (in ald; cald, almd and as-types); the abc transporter domain

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.Arg660Leu Pathogenic ★ same residue
ABCD1 p.Arg660Gln 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-arg660trp (accessed [today's date]).

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