Is EFCAB6 p.Ser970Thr (c.2909G>C) pathogenic?

EFCAB6 p.Ser970Thr (c.2909G>C) is classified Uncertain significance in EFCAB6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-14). AlphaMissense: likely benign (0.0914); Very rare (popmax 0.00585%, nfe).

How common is EFCAB6 p.Ser970Thr (c.2909G>C) in the general population?

EFCAB6 p.Ser970Thr (c.2909G>C) is very rare (popmax 0.00585%, nfe) (gnomAD).

What do computational predictors say about EFCAB6 p.Ser970Thr (c.2909G>C)?

AlphaMissense predicts likely benign (score 0.0914) — an in-silico prediction, not a clinical call.

EFCAB6 p.Ser970Thr

c.2909G>C · VCV3506915

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0914 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00585%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0914	likely benign
REVEL	0.403	indeterminate
SaProt	LLR -7.14	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.98	GERP -2.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 253 kb · p 0.5 · regional, not allelic
Overall
CADD	16.24	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 0.00585% European (non-Finnish) · 69/1,179,976 alleles

Filtering AF 0.0047% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00431%

Overall 0.00446% 72/1,613,914 alleles · very rare exomes 67/1,461,722 · genomes 5/152,192 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00585%	17,101
Remaining individualsnot grpmax-eligible	0.0032%	31,238
African / African-American	0.00133%	74,916

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: EFCAB6
Protein: p.Ser970Thr
Coding: c.2909G>C
MANE Select: NM_022785
Type: single nucleotide variant
Location: chr22:43590197 (GRCh38)
Gene constraint: LOEUF 1.013 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.65 · 2 PDB
Residue 970: the ef-hand 11 domain

Full EFCAB6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFCAB6 p.Ala1038Val Uncertain significance ★ ⚠ same type
EFCAB6 p.Ala1168Gly Uncertain significance ★ ⚠ same type
EFCAB6 p.Ala1203Val Uncertain significance ★ ⚠ same type
EFCAB6 p.Ala1296Glu Uncertain significance ★ ⚠ same type
EFCAB6 p.Ala1424Gly Uncertain significance ★ ⚠ same type
EFCAB6 p.Ala1457Val Uncertain significance ★ ⚠ same type
EFCAB6 p.Ala567Pro Uncertain significance ★ ⚠ same type
EFCAB6 p.Ala728Thr 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/efcab6-p-ser970thr (accessed [today's date]).

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