Is ABCD1 p.Arg308Cys (c.922C>T) pathogenic?

ABCD1 p.Arg308Cys (c.922C>T) is classified Conflicting classifications of pathogenicity in ABCD1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-10-29). AlphaMissense: likely benign (0.1067); Ultra-rare (popmax 0.0109%, amr); Associated with Inborn genetic diseases.

What condition is associated with ABCD1 p.Arg308Cys (c.922C>T)?

ABCD1 p.Arg308Cys (c.922C>T) is associated with Inborn genetic diseases, adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Arg308Cys (c.922C>T) in the general population?

ABCD1 p.Arg308Cys (c.922C>T) is ultra-rare (popmax 0.0109%, amr) (gnomAD).

What do computational predictors say about ABCD1 p.Arg308Cys (c.922C>T)?

AlphaMissense predicts likely benign (score 0.1067) — an in-silico prediction, not a clinical call.

ABCD1 p.Arg308Cys

c.922C>T · rs782419107 · VCV850748

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1067 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0109%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1067	likely benign
REVEL	0.434	indeterminate
SaProt	LLR -10.41	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -3.5, phastCons 0.99
Regional constraint	o/e 0.69	unconstrained · MANE · 14 kb · p 4.8e-06 · regional, not allelic
Overall
CADD	21.8	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 0.0109% Admixed American · 5/45,969 alleles

Filtering AF 0.00426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0027%

Overall 0.00124% 15/1,210,936 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0109%	9,194
South Asian	0.00176%	56,910
European (non-Finnish)	0.00101%	99,485

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.Arg308Cys
Coding: c.922C>T
MANE Select: NM_000033
dbSNP: rs782419107
Type: single nucleotide variant
Location: chrX:153729253 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 308: an α-helix; 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.Arg308Pro Uncertain significance ★ ⚠ same residue
ABCD1 p.Arg308= Likely benign ★ same residue
ABCD1 p.Arg308His 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

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-arg308cys (accessed [today's date]).

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