Is EFCAB14 p.Val319Ala (c.956T>C) pathogenic?

EFCAB14 p.Val319Ala (c.956T>C) is classified Uncertain significance in EFCAB14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). AlphaMissense: likely benign (0.0756); Ultra-rare (popmax 0.0141%, nfe).

How common is EFCAB14 p.Val319Ala (c.956T>C) in the general population?

EFCAB14 p.Val319Ala (c.956T>C) is ultra-rare (popmax 0.0141%, nfe) (gnomAD).

What do computational predictors say about EFCAB14 p.Val319Ala (c.956T>C)?

AlphaMissense predicts likely benign (score 0.0756) — an in-silico prediction, not a clinical call.

EFCAB14 p.Val319Ala

c.956T>C · VCV3843566

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0756 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0141%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0756	likely benign
REVEL	0.267	benign-leaning
SaProt	LLR -4.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.91	GERP 2, phastCons 0.75
Regional constraint	o/e 0.93	unconstrained · MANE · 40 kb · p 0.079 · regional, not allelic
Overall
CADD	17.35	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

Grpmax group 0.0141% European (non-Finnish) · 166/1,179,900 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0116%

Overall 0.0108% 175/1,613,840 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0141%	7,108
Remaining individualsnot grpmax-eligible	0.0096%	10,412
African / African-American	0.00401%	24,963

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: EFCAB14
Protein: p.Val319Ala
Coding: c.956T>C
MANE Select: NM_014774
Type: single nucleotide variant
Location: chr1:46688384 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.45

Full EFCAB14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFCAB14 p.Ala196Thr Uncertain significance ★ ⚠ same type
EFCAB14 p.Ala393Thr Uncertain significance ★ ⚠ same type
EFCAB14 p.Ala423Val Uncertain significance ★ ⚠ same type
EFCAB14 p.Ala87Val Uncertain significance ★ same type
EFCAB14 p.Arg110Gln Uncertain significance ★ ⚠ same type
EFCAB14 p.Arg33Leu Uncertain significance ★ ⚠ same type
EFCAB14 p.Arg388Ser Uncertain significance ★ ⚠ same type
EFCAB14 p.Asn127Lys 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/efcab14-p-val319ala (accessed [today's date]).

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