Is ECT2 p.Ile679Val (c.2035A>G) pathogenic?

ECT2 p.Ile679Val (c.2035A>G) is classified Likely benign in ECT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-16). AlphaMissense: likely benign (0.0546); Ultra-rare (popmax 0.0817%, amr).

How common is ECT2 p.Ile679Val (c.2035A>G) in the general population?

ECT2 p.Ile679Val (c.2035A>G) is ultra-rare (popmax 0.0817%, amr) (gnomAD).

What do computational predictors say about ECT2 p.Ile679Val (c.2035A>G)?

AlphaMissense predicts likely benign (score 0.0546) — an in-silico prediction, not a clinical call.

ECT2 p.Ile679Val

c.2035A>G · VCV3506567

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0546 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0817%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0546	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -4.67	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 -0.98	GERP -3.3
Regional constraint	o/e 0.87	unconstrained · MANE · 66 kb · p 1.6e-05 · regional, not allelic
Overall
CADD	10.2	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

Grpmax group 0.0817% Admixed American · 49/59,960 alleles

Filtering AF 0.0635% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.057%

Overall 0.00459% 74/1,613,206 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0817%	1,224
East Asian	0.0067%	14,921
African / African-American	0.00267%	37,449
European (non-Finnish)	0.00161%	62,082
Remaining individualsnot grpmax-eligible	0.0016%	62,432

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.Ile679Val
Coding: c.2035A>G
MANE Select: NM_001258315
Type: single nucleotide variant
Location: chr3:172802909 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.17 · 3 PDB
Residue 679: a β-strand; 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-ile679val (accessed [today's date]).

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