Is ECT2 p.Val590Asp (c.1769T>A) pathogenic?

ECT2 p.Val590Asp (c.1769T>A) is classified Uncertain significance in ECT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely pathogenic (0.6652); Very rare (popmax 0.00133%, afr).

How common is ECT2 p.Val590Asp (c.1769T>A) in the general population?

ECT2 p.Val590Asp (c.1769T>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ECT2 p.Val590Asp (c.1769T>A)?

AlphaMissense predicts likely pathogenic (score 0.6652) — an in-silico prediction, not a clinical call.

ECT2 p.Val590Asp

c.1769T>A · VCV4246498

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6652 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6652	likely pathogenic
REVEL	0.267	benign-leaning
SaProt	LLR -9.95	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	Δ0.20	donor gain · deltas
Constraint at this position
Conservation	phyloP 2.8	GERP 0.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 66 kb · p 1.6e-05 · regional, not allelic
Overall
CADD	23.4	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 0.00133% African / African-American · 1/74,924 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,613,562 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,924
European (non-Finnish)	0.000339%	294,904

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.Val590Asp
Coding: c.1769T>A
MANE Select: NM_001258315
Type: single nucleotide variant
Location: chr3:172784747 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.17 · 3 PDB
Residue 590: the dh domain; an α-helix

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-val590asp (accessed [today's date]).

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