Is EFCAB3 p.Pro272Ala (c.814C>G) pathogenic?

EFCAB3 p.Pro272Ala (c.814C>G) is classified Uncertain significance in EFCAB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-27). AlphaMissense: likely benign (0.2514); Rare (popmax 0.219%, afr).

How common is EFCAB3 p.Pro272Ala (c.814C>G) in the general population?

EFCAB3 p.Pro272Ala (c.814C>G) is rare (popmax 0.219%, afr) (gnomAD).

What do computational predictors say about EFCAB3 p.Pro272Ala (c.814C>G)?

AlphaMissense predicts likely benign (score 0.2514) — an in-silico prediction, not a clinical call.

EFCAB3 p.Pro272Ala

c.814C>G · rs115042128 · VCV3087429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2514 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.219%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2514	likely benign
REVEL	0.481	indeterminate
SaProt	LLR -7.13	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 33 kb · p 0.00011 · regional, not allelic
Overall
CADD	23.8	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 0.219% African / African-American · 163/74,434 alleles

Filtering AF 0.191% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.181%

Overall 0.0277% 444/1,603,962 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.219%	457
Middle Eastern	0.0665%	1,503
South Asian	0.0554%	1,804
Admixed American	0.0467%	2,140
Remaining individualsnot grpmax-eligible	0.029%	3,451
European (non-Finnish)	0.0151%	6,610
East Asian	0.00896%	11,163
Ashkenazi Jewishnot grpmax-eligible	0.00342%	29,204

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: EFCAB3
Protein: p.Pro272Ala
Coding: c.814C>G
MANE Select: NM_173503
dbSNP: rs115042128
Type: single nucleotide variant
Location: chr17:62407159 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.80

Full EFCAB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFCAB3 p.Pro272Thr Uncertain significance ★ ⚠ same residue
EFCAB3 c.34+6G>T Benign ★★ same type
EFCAB3 c.488+2T>C Benign ★★ same type
EFCAB3 p.Arg99Ter Benign/Likely benign ★★ same type
EFCAB3 p.Lys15Asn Benign ★★ same type
EFCAB3 p.Ser370Phe Benign ★★ same type
EFCAB3 c.-5G>A Uncertain significance ★ same type
EFCAB3 c.-8C>G 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/efcab3-p-pro272ala (accessed [today's date]).

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