Is EFCAB12 p.Pro36Arg (c.107C>G) pathogenic?

EFCAB12 p.Pro36Arg (c.107C>G) is classified Uncertain significance in EFCAB12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-11). AlphaMissense: likely benign (0.0629); Very rare (popmax 0.00178%, nfe).

How common is EFCAB12 p.Pro36Arg (c.107C>G) in the general population?

EFCAB12 p.Pro36Arg (c.107C>G) is very rare (popmax 0.00178%, nfe) (gnomAD).

What do computational predictors say about EFCAB12 p.Pro36Arg (c.107C>G)?

AlphaMissense predicts likely benign (score 0.0629) — an in-silico prediction, not a clinical call.

EFCAB12 p.Pro36Arg

c.107C>G · rs58932597 · VCV2541349

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0629 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0629	likely benign
REVEL	0.003	strongly benign-leaning
SaProt	LLR -10.67	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.97 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.7	GERP -4.7
Regional constraint	o/e 0.88	unconstrained · MANE · 27 kb · p 0.0017 · regional, not allelic
Overall
CADD	0.001	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 0.00178% European (non-Finnish) · 21/1,179,832 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.0013% 21/1,613,616 alleles · very rare

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: EFCAB12
Protein: p.Pro36Arg
Coding: c.107C>G
MANE Select: NM_207307
dbSNP: rs58932597
Type: single nucleotide variant
Location: chr3:129421746 (GRCh38)
Gene constraint: LOEUF 1.061 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.48
Residue 36: a UniProt-annotated variant site (in)

Full EFCAB12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFCAB12 p.Ala137Gly Uncertain significance ★ ⚠ same type
EFCAB12 p.Ala223Val Uncertain significance ★ ⚠ same type
EFCAB12 p.Ala277Ser Uncertain significance ★ ⚠ same type
EFCAB12 p.Ala39Thr Uncertain significance ★ ⚠ same type
EFCAB12 p.Ala417Asp Uncertain significance ★ ⚠ same type
EFCAB12 p.Ala453Thr Uncertain significance ★ ⚠ same type
EFCAB12 p.Ala542Val Uncertain significance ★ ⚠ same type
EFCAB12 p.Ala561Thr 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/efcab12-p-pro36arg (accessed [today's date]).

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