Is ABCD3 p.Val94Met (c.280G>A) pathogenic?

ABCD3 p.Val94Met (c.280G>A) is classified Uncertain significance in ABCD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-07). AlphaMissense: likely benign (0.2265); Ultra-rare (popmax 0.0469%, eas).

How common is ABCD3 p.Val94Met (c.280G>A) in the general population?

ABCD3 p.Val94Met (c.280G>A) is ultra-rare (popmax 0.0469%, eas) (gnomAD).

What do computational predictors say about ABCD3 p.Val94Met (c.280G>A)?

AlphaMissense predicts likely benign (score 0.2265) — an in-silico prediction, not a clinical call.

ABCD3 p.Val94Met

c.280G>A · VCV3881363

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2265 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0469%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2265	likely benign
REVEL	0.753	pathogenic-leaning
SaProt	LLR -10.13	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 23 kb · p 3.7e-09 · regional, not allelic
Overall
CADD	25.1	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 0.0469% East Asian · 21/44,788 alleles

Filtering AF 0.0314% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0263%

Overall 0.00157% 23/1,461,248 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0469%	2,133
Remaining individualsnot grpmax-eligible	0.0016%	62,484
South Asian	0.0011%	91,056

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: ABCD3
Protein: p.Val94Met
Coding: c.280G>A
MANE Select: NM_002858
Type: single nucleotide variant
Location: chr1:94467952 (GRCh38)
Gene constraint: LOEUF 0.484 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 83.39 · 9 PDB
Residue 94: an α-helix; the abc transmembrane type-1 domain

Full ABCD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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ABCD3 p.Ala3Val Uncertain significance ★★ ⚠ same type
ABCD3 p.Arg496Cys Uncertain significance ★★ ⚠ same type
ABCD3 p.Asn12Tyr Uncertain significance ★★ ⚠ same type
ABCD3 p.Ile225Val Uncertain significance ★★ ⚠ same type
ABCD3 p.Leu23Val Uncertain significance ★★ ⚠ same type
ABCD3 p.Leu45Val Uncertain significance ★★ ⚠ same type
ABCD3 p.Pro425Leu Uncertain significance ★★ ⚠ same type

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/abcd3-p-val94met (accessed [today's date]).

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