Is ABCD1 p.Arg74Gln (c.221G>A) pathogenic?

ABCD1 p.Arg74Gln (c.221G>A) is classified Uncertain significance in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-09-12). AlphaMissense: likely benign (0.1083); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ABCD1 p.Arg74Gln (c.221G>A)?

ABCD1 p.Arg74Gln (c.221G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ABCD1 p.Arg74Gln (c.221G>A) in the general population?

ABCD1 p.Arg74Gln (c.221G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCD1 p.Arg74Gln (c.221G>A)?

AlphaMissense predicts likely benign (score 0.1083) — an in-silico prediction, not a clinical call.

ABCD1 p.Arg74Gln

c.221G>A · rs868953385 · VCV1787907

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1083 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,160,494)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1083	likely benign
REVEL	0.57	indeterminate
SaProt	LLR -5.55	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 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 865 bp · p 0.3 · regional, not allelic
Overall
CADD	18.67	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,160,494). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABCD1
Protein: p.Arg74Gln
Coding: c.221G>A
MANE Select: NM_000033
dbSNP: rs868953385
Type: single nucleotide variant
Location: chrX:153725487 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 74: an α-helix; the 'interaction with pex19' region; the 'pex19 binding site and required for peroxisomal targeting' region

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

Similar variants

ABCD1 p.Arg74Trp Likely pathogenic ★★ same residue
ABCD1 p.Arg74Leu Likely pathogenic ★ same residue
ABCD1 c.1635-2A>G Pathogenic ★★ same condition
ABCD1 c.1866-10G>A Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Arg163His Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Arg189Trp Pathogenic/Likely pathogenic ★★ same condition
ABCD1 p.Gly266Arg Pathogenic ★★ ⚠ same condition
ABCD1 p.Ser262Trp Pathogenic/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-arg74gln (accessed [today's date]).

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