Is EFCC1 p.Arg134Pro (c.401G>C) pathogenic?

EFCC1 p.Arg134Pro (c.401G>C) is classified Uncertain significance in EFCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-22). AlphaMissense: likely benign (0.3276); Ultra-rare (popmax 0.0171%, mid).

How common is EFCC1 p.Arg134Pro (c.401G>C) in the general population?

EFCC1 p.Arg134Pro (c.401G>C) is ultra-rare (popmax 0.0171%, mid) (gnomAD).

What do computational predictors say about EFCC1 p.Arg134Pro (c.401G>C)?

AlphaMissense predicts likely benign (score 0.3276) — an in-silico prediction, not a clinical call.

EFCC1 p.Arg134Pro

c.401G>C · rs2529561828 · VCV2620918

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3276 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0171%, mid)

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	0.3276	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -8.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2	GERP -1.2, phastCons 0.17
Regional constraint	o/e 0.97	unconstrained · MANE · 38 kb · p 0.3 · regional, not allelic
Overall
CADD	15.75	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 0.0171% Middle Eastern · 1/5,834 alleles

Filtering AF 7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000259% 4/1,544,200 alleles · ultra-rare exomes 4/1,392,046 · genomes 0/152,154 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0171%	5,834
European (non-Finnish)	0.000262%	381,559

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.Arg134Pro
Coding: c.401G>C
MANE Select: NM_001377500
dbSNP: rs2529561828
Type: single nucleotide variant
Location: chr3:129002029 (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-arg134pro (accessed [today's date]).

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