Is ABCD1 p.Arg37Cys (c.109C>T) pathogenic?

ABCD1 p.Arg37Cys (c.109C>T) is classified Conflicting classifications of pathogenicity in ABCD1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-06). AlphaMissense: likely benign (0.1195); Very rare (popmax 0.00269%, amr); Associated with Inborn genetic diseases.

What condition is associated with ABCD1 p.Arg37Cys (c.109C>T)?

ABCD1 p.Arg37Cys (c.109C>T) is associated with Inborn genetic diseases, adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Arg37Cys (c.109C>T) in the general population?

ABCD1 p.Arg37Cys (c.109C>T) is very rare (popmax 0.00269%, amr) (gnomAD).

What do computational predictors say about ABCD1 p.Arg37Cys (c.109C>T)?

AlphaMissense predicts likely benign (score 0.1195) — an in-silico prediction, not a clinical call.

ABCD1 p.Arg37Cys

c.109C>T · rs1479670923 · VCV2562088

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1195 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00269%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1195	likely benign
REVEL	0.47	indeterminate
SaProt	LLR -9.14	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 865 bp · p 0.3 · regional, not allelic
Overall
CADD	20.2	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 0.00269% Admixed American · 1/37,173 alleles

Filtering AF 9.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.6e-05%

Overall 0.000436% 5/1,147,471 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00269%	37,173
Remaining individualsnot grpmax-eligible	0.00222%	44,991
European (non-Finnish)	0.000347%	288,062

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.Arg37Cys
Coding: c.109C>T
MANE Select: NM_000033
dbSNP: rs1479670923
Type: single nucleotide variant
Location: chrX:153725375 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB

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.Arg37Leu Uncertain significance ★★ ⚠ same residue
ABCD1 p.Arg37Pro Uncertain significance ★ ⚠ 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-arg37cys (accessed [today's date]).

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