Is ECT2 p.Gly712Ser (c.2134G>A) pathogenic?

ECT2 p.Gly712Ser (c.2134G>A) is classified Uncertain significance in ECT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-30). AlphaMissense: likely benign (0.0793); Ultra-rare (popmax 0.035%, amr).

How common is ECT2 p.Gly712Ser (c.2134G>A) in the general population?

ECT2 p.Gly712Ser (c.2134G>A) is ultra-rare (popmax 0.035%, amr) (gnomAD).

What do computational predictors say about ECT2 p.Gly712Ser (c.2134G>A)?

AlphaMissense predicts likely benign (score 0.0793) — an in-silico prediction, not a clinical call.

ECT2 p.Gly712Ser

c.2134G>A · VCV3506564

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0793 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0793	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -6.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.31	acceptor loss, 27 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 66 kb · p 1.6e-05 · regional, not allelic
Overall
CADD	20.5	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 0.035% Admixed American · 21/59,942 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.0018% 29/1,613,280 alleles · ultra-rare exomes 25/1,461,420 · genomes 4/151,860 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.035%	2,854
Remaining individualsnot grpmax-eligible	0.0016%	62,452
European (non-Finnish)	0.000593%	168,531

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: ECT2
Protein: p.Gly712Ser
Coding: c.2134G>A
MANE Select: NM_001258315
Type: single nucleotide variant
Location: chr3:172805758 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.17 · 3 PDB
Residue 712: the ph domain

Full ECT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECT2 p.His912Arg Uncertain significance ★★ ⚠ same type
ECT2 p.Pro236Ala Uncertain significance ★★ ⚠ same type
ECT2 p.Pro481= Benign ★★ same type
ECT2 c.1069-2A>G Uncertain significance ★ same type
ECT2 p.Ala258Thr Uncertain significance ★ ⚠ same type
ECT2 p.Ala850Thr Uncertain significance ★ ⚠ same type
ECT2 p.Arg169Cys Uncertain significance ★ ⚠ same type
ECT2 p.Arg194Met 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/ect2-p-gly712ser (accessed [today's date]).

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