Is EFCAB5 p.Glu699= (c.2097A>G) pathogenic?

EFCAB5 p.Glu699= (c.2097A>G) is classified Likely benign in EFCAB5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). Ultra-rare (popmax 0.0435%, amr).

How common is EFCAB5 p.Glu699= (c.2097A>G) in the general population?

EFCAB5 p.Glu699= (c.2097A>G) is ultra-rare (popmax 0.0435%, amr) (gnomAD).

EFCAB5 p.Glu699=

c.2097A>G · rs756574322 · VCV2647621

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0435%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -0.47, phastCons 0.81
Overall
CADD	5.438	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0435% Admixed American · 25/57,526 alleles

Filtering AF 0.0302% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0258%

Overall 0.00662% 106/1,602,178 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0435%	2,301
Middle Eastern	0.0331%	3,024
Remaining individualsnot grpmax-eligible	0.0177%	5,652
Finnishnot grpmax-eligible	0.00787%	12,713
European (non-Finnish)	0.00528%	18,928
Ashkenazi Jewishnot grpmax-eligible	0.00341%	29,324

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.Glu699=
Coding: c.2097A>G
MANE Select: NM_198529
dbSNP: rs756574322
Type: single nucleotide variant
Location: chr17:30054051 (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-glu699 (accessed [today's date]).

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