Is EFCAB13 p.Pro756Ser (c.2266C>T) pathogenic?

EFCAB13 p.Pro756Ser (c.2266C>T) is classified Uncertain significance in EFCAB13 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-15). AlphaMissense: likely pathogenic (0.5648); Absent from gnomAD v4.1.

How common is EFCAB13 p.Pro756Ser (c.2266C>T) in the general population?

EFCAB13 p.Pro756Ser (c.2266C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFCAB13 p.Pro756Ser (c.2266C>T)?

AlphaMissense predicts likely pathogenic (score 0.5648) — an in-silico prediction, not a clinical call.

EFCAB13 p.Pro756Ser

c.2266C>T · VCV3843555

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5648 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5648	likely pathogenic · top 5% in EFCAB13
REVEL	0.043	moderately benign-leaning
SaProt	LLR -7.64	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.73	phastCons 0.86
Regional constraint	o/e 0.86	unconstrained · MANE · 112 kb · p 6e-06 · regional, not allelic
Overall
CADD	13.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EFCAB13
Protein: p.Pro756Ser
Coding: c.2266C>T
MANE Select: NM_152347
Type: single nucleotide variant
Location: chr17:47409679 (GRCh38)
Gene constraint: LOEUF 0.953 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
Structure: AlphaFold pLDDT 53.37
Residue 756: the ef-hand 4 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-pro756ser (accessed [today's date]).

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