Is EFCAB13 p.Val261Ala (c.782T>C) pathogenic?

EFCAB13 p.Val261Ala (c.782T>C) is classified Uncertain significance in EFCAB13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: ambiguous (0.3755); Very rare (popmax 0.00678%, amr).

How common is EFCAB13 p.Val261Ala (c.782T>C) in the general population?

EFCAB13 p.Val261Ala (c.782T>C) is very rare (popmax 0.00678%, amr) (gnomAD).

What do computational predictors say about EFCAB13 p.Val261Ala (c.782T>C)?

AlphaMissense predicts ambiguous (score 0.3755) — an in-silico prediction, not a clinical call.

EFCAB13 p.Val261Ala

c.782T>C · VCV4246885

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3755 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00678%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3755	ambiguous
REVEL	0.108	moderately benign-leaning
SaProt	LLR -9.75	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 112 kb · p 6e-06 · regional, not allelic
Overall
CADD	14.21	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 0.00678% Admixed American · 4/59,036 alleles

Filtering AF 0.00228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000624% 10/1,601,608 alleles · very rare exomes 9/1,458,876 · genomes 1/142,732 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00678%	14,759
East Asian	0.00224%	44,728
Remaining individualsnot grpmax-eligible	0.00161%	62,208
European (non-Finnish)	0.000341%	293,589

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: EFCAB13
Protein: p.Val261Ala
Coding: c.782T>C
MANE Select: NM_152347
Type: single nucleotide variant
Location: chr17:47361498 (GRCh38)
Gene constraint: LOEUF 0.953 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
Structure: AlphaFold pLDDT 53.37

Full EFCAB13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFCAB13 p.Ala453Val Uncertain significance ★ ⚠ same type
EFCAB13 p.Ala605Gly Uncertain significance ★ ⚠ same type
EFCAB13 p.Ala668Asp Uncertain significance ★ ⚠ same type
EFCAB13 p.Ala680Val Uncertain significance ★ ⚠ same type
EFCAB13 p.Ala750Ser Uncertain significance ★ ⚠ same type
EFCAB13 p.Arg185Gln Uncertain significance ★ ⚠ same type
EFCAB13 p.Arg236Gln Uncertain significance ★ ⚠ same type
EFCAB13 p.Arg255Cys 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/efcab13-p-val261ala (accessed [today's date]).

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