Is EFCAB7 p.Pro18Arg (c.53C>G) pathogenic?

EFCAB7 p.Pro18Arg (c.53C>G) is classified Uncertain significance in EFCAB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). AlphaMissense: likely benign (0.0712); Very rare (popmax 0.00452%, eas).

How common is EFCAB7 p.Pro18Arg (c.53C>G) in the general population?

EFCAB7 p.Pro18Arg (c.53C>G) is very rare (popmax 0.00452%, eas) (gnomAD).

What do computational predictors say about EFCAB7 p.Pro18Arg (c.53C>G)?

AlphaMissense predicts likely benign (score 0.0712) — an in-silico prediction, not a clinical call.

EFCAB7 p.Pro18Arg

c.53C>G · VCV3506940

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0712 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00452%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0712	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -6.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.17	GERP -3.5, phastCons 0.016
Regional constraint	o/e 0.87	unconstrained · MANE · 47 kb · p 0.00062 · regional, not allelic
Overall
CADD	0.153	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 0.00452% East Asian · 2/44,204 alleles

Filtering AF 0.00075% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000281%

Overall 0.000125% 2/1,596,504 alleles · very rare exomes 2/1,444,274 · genomes 0/152,230 · joint denominator

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: EFCAB7
Protein: p.Pro18Arg
Coding: c.53C>G
MANE Select: NM_032437
Type: single nucleotide variant
Location: chr1:63525625 (GRCh38)
Gene constraint: LOEUF 1.112 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.62
Residue 18: the 'disordered' region

Full EFCAB7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFCAB7 p.Pro18Ser Uncertain significance ★ ⚠ same residue
EFCAB7 p.Phe279Cys Uncertain significance ★★ same type
EFCAB7 p.Asp571Glu Benign ★★ same type
EFCAB7 p.Ser186Gly Benign ★★ same type
EFCAB7 p.Ala472Val Uncertain significance ★ ⚠ same type
EFCAB7 p.Ala9Thr Uncertain significance ★ ⚠ same type
EFCAB7 p.Arg203Trp Uncertain significance ★ ⚠ same type
EFCAB7 p.Arg461Gly 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/efcab7-p-pro18arg (accessed [today's date]).

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