Is ABCD3 p.Met313Val (c.937A>G) pathogenic?

ABCD3 p.Met313Val (c.937A>G) is classified Uncertain significance in ABCD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-22). AlphaMissense: likely benign (0.1412); Ultra-rare (popmax 0.03%, amr).

How common is ABCD3 p.Met313Val (c.937A>G) in the general population?

ABCD3 p.Met313Val (c.937A>G) is ultra-rare (popmax 0.03%, amr) (gnomAD).

What do computational predictors say about ABCD3 p.Met313Val (c.937A>G)?

AlphaMissense predicts likely benign (score 0.1412) — an in-silico prediction, not a clinical call.

ABCD3 p.Met313Val

c.937A>G · rs564987217 · VCV2187484

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1412 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1412	likely benign
REVEL	0.735	pathogenic-leaning
SaProt	LLR -3.09	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	Δ0.32	acceptor gain · deltas
Pangolin	Δ0.25	loss · gain 0.15 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 23 kb · p 3.7e-09 · regional, not allelic
Overall
CADD	26.5	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 0.03% Admixed American · 18/59,990 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00378% 61/1,613,748 alleles · ultra-rare exomes 57/1,461,596 · genomes 4/152,152 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.03%	3,333
East Asian	0.00669%	14,949
European (non-Finnish)	0.00305%	32,775
South Asian	0.0022%	45,538
Remaining individualsnot grpmax-eligible	0.0016%	62,460
African / African-American	0.00134%	74,906

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.Met313Val
Coding: c.937A>G
MANE Select: NM_002858
dbSNP: rs564987217
Type: single nucleotide variant
Location: chr1:94487581 (GRCh38)
Gene constraint: LOEUF 0.484 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 83.39 · 9 PDB
Residue 313: the abc transmembrane type-1 domain; an α-helix

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

Similar variants

ABCD3 p.Met313Leu Uncertain significance ★ ⚠ same residue
ABCD3 p.Ala131Thr Uncertain significance ★★ ⚠ same type
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

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-met313val (accessed [today's date]).

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