Is EFCAB13 p.Pro524Ser (c.1570C>T) pathogenic?

EFCAB13 p.Pro524Ser (c.1570C>T) is classified Uncertain significance in EFCAB13 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: likely benign (0.1045); Ultra-rare (popmax 0.0967%, sas).

How common is EFCAB13 p.Pro524Ser (c.1570C>T) in the general population?

EFCAB13 p.Pro524Ser (c.1570C>T) is ultra-rare (popmax 0.0967%, sas) (gnomAD).

What do computational predictors say about EFCAB13 p.Pro524Ser (c.1570C>T)?

AlphaMissense predicts likely benign (score 0.1045) — an in-silico prediction, not a clinical call.

EFCAB13 p.Pro524Ser

c.1570C>T · rs371862264 · VCV2562194

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1045 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0967%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1045	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -4.72	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 -2
Regional constraint	o/e 0.86	unconstrained · MANE · 112 kb · p 6e-06 · regional, not allelic
Overall
CADD	0.358	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 0.0967% South Asian · 88/91,004 alleles

Filtering AF 0.0803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0743%

Overall 0.00639% 103/1,612,466 alleles · ultra-rare exomes 98/1,460,366 · genomes 5/152,100 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0967%	1,034
Middle Eastern	0.0164%	6,080
Remaining individualsnot grpmax-eligible	0.00481%	20,806
African / African-American	0.00134%	74,862
European (non-Finnish)	0.000848%	117,893

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: EFCAB13
Protein: p.Pro524Ser
Coding: c.1570C>T
MANE Select: NM_152347
dbSNP: rs371862264
Type: single nucleotide variant
Location: chr17:47379241 (GRCh38)
Gene constraint: LOEUF 0.953 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
Structure: AlphaFold pLDDT 53.37
Residue 524: the ef-hand 2 domain

Full EFCAB13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFCAB13 p.Ala453Val Uncertain significance ★ ⚠ same type
EFCAB13 p.Ala605Gly Uncertain significance ★ ⚠ same type
EFCAB13 p.Ala668Asp Uncertain significance ★ ⚠ same type
EFCAB13 p.Ala680Val Uncertain significance ★ ⚠ same type
EFCAB13 p.Ala750Ser Uncertain significance ★ ⚠ same type
EFCAB13 p.Arg185Gln Uncertain significance ★ ⚠ same type
EFCAB13 p.Arg236Gln Uncertain significance ★ ⚠ same type
EFCAB13 p.Arg255Cys 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/efcab13-p-pro524ser (accessed [today's date]).

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