Is EFCAB5 p.Leu930Phe (c.2790G>T) pathogenic?

EFCAB5 p.Leu930Phe (c.2790G>T) is classified Uncertain significance in EFCAB5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: ambiguous (0.3498); Very rare (popmax 0.00668%, afr).

How common is EFCAB5 p.Leu930Phe (c.2790G>T) in the general population?

EFCAB5 p.Leu930Phe (c.2790G>T) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about EFCAB5 p.Leu930Phe (c.2790G>T)?

AlphaMissense predicts ambiguous (score 0.3498) — an in-silico prediction, not a clinical call.

EFCAB5 p.Leu930Phe

c.2790G>T · VCV4246939

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3498 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3498	ambiguous
REVEL	0.137	moderately benign-leaning
SaProt	LLR -9.83	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 0.26	GERP -1.3, phastCons 0.92
Regional constraint	o/e 0.95	unconstrained · MANE · 166 kb · p 0.049 · regional, not allelic
Overall
CADD	19.07	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 0.00668% African / African-American · 5/74,900 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000372% 6/1,613,772 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,980
Finnishnot grpmax-eligible	0.00156%	64,014

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: EFCAB5
Protein: p.Leu930Phe
Coding: c.2790G>T
MANE Select: NM_198529
Type: single nucleotide variant
Location: chr17:30078267 (GRCh38)
Gene constraint: LOEUF 0.908 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.22

Full EFCAB5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFCAB5 p.Ala1262Pro Uncertain significance ★ same type
EFCAB5 p.Ala128Thr Uncertain significance ★ ⚠ same type
EFCAB5 p.Ala1493Val Uncertain significance ★ ⚠ same type
EFCAB5 p.Ala373Val Uncertain significance ★ ⚠ same type
EFCAB5 p.Ala514Thr Uncertain significance ★ ⚠ same type
EFCAB5 p.Ala5Pro Uncertain significance ★ ⚠ same type
EFCAB5 p.Arg1158Gln Uncertain significance ★ ⚠ same type
EFCAB5 p.Arg1329Gln 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/efcab5-p-leu930phe (accessed [today's date]).

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