Is EFCAB7 p.Pro18Ser (c.52C>T) pathogenic?

EFCAB7 p.Pro18Ser (c.52C>T) is classified Uncertain significance in EFCAB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-02). AlphaMissense: likely benign (0.0687); Ultra-rare (popmax 0.0246%, afr).

How common is EFCAB7 p.Pro18Ser (c.52C>T) in the general population?

EFCAB7 p.Pro18Ser (c.52C>T) is ultra-rare (popmax 0.0246%, afr) (gnomAD).

What do computational predictors say about EFCAB7 p.Pro18Ser (c.52C>T)?

AlphaMissense predicts likely benign (score 0.0687) — an in-silico prediction, not a clinical call.

EFCAB7 p.Pro18Ser

c.52C>T · rs139665471 · VCV2513624

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0687 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0246%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0687	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -7.20	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 -1.1
Regional constraint	o/e 0.87	unconstrained · MANE · 47 kb · p 0.00062 · regional, not allelic
Overall
CADD	1.748	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 0.0246% African / African-American · 18/73,238 alleles

Filtering AF 0.0158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0131%

Overall 0.00163% 26/1,595,520 alleles · ultra-rare exomes 13/1,443,432 · genomes 13/152,088 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0246%	4,069
Remaining individualsnot grpmax-eligible	0.00971%	10,298
Admixed American	0.00188%	53,298
European (non-Finnish)	8.5e-05%	1,176,004

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.Pro18Ser
Coding: c.52C>T
MANE Select: NM_032437
dbSNP: rs139665471
Type: single nucleotide variant
Location: chr1:63525624 (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.Pro18Arg 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-pro18ser (accessed [today's date]).

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