Is EFCC1 p.Pro3Ala (c.7C>G) pathogenic?

EFCC1 p.Pro3Ala (c.7C>G) is classified Uncertain significance in EFCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-29). AlphaMissense: likely benign (0.0457); Ultra-rare (popmax 0.023%, afr).

How common is EFCC1 p.Pro3Ala (c.7C>G) in the general population?

EFCC1 p.Pro3Ala (c.7C>G) is ultra-rare (popmax 0.023%, afr) (gnomAD).

What do computational predictors say about EFCC1 p.Pro3Ala (c.7C>G)?

AlphaMissense predicts likely benign (score 0.0457) — an in-silico prediction, not a clinical call.

EFCC1 p.Pro3Ala

c.7C>G · VCV4016498

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0457 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.023%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0457	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -5.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.65	GERP 0.59
Regional constraint	o/e 0.97	unconstrained · MANE · 38 kb · p 0.3 · regional, not allelic
Overall
CADD	19.38	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 0.023% African / African-American · 15/65,106 alleles

Filtering AF 0.0142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.00117% 16/1,364,172 alleles · ultra-rare exomes 5/1,211,974 · genomes 11/152,198 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.023%	4,340
Admixed American	0.00372%	26,908

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: EFCC1
Protein: p.Pro3Ala
Coding: c.7C>G
MANE Select: NM_001377500
Type: single nucleotide variant
Location: chr3:129001635 (GRCh38)

Full EFCC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/efcc1-p-pro3ala (accessed [today's date]).

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