Is ECT2 p.Arg675Gln (c.2024G>A) pathogenic?

ECT2 p.Arg675Gln (c.2024G>A) is classified Uncertain significance in ECT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). AlphaMissense: likely benign (0.1849); Ultra-rare (popmax 0.0331%, mid).

How common is ECT2 p.Arg675Gln (c.2024G>A) in the general population?

ECT2 p.Arg675Gln (c.2024G>A) is ultra-rare (popmax 0.0331%, mid) (gnomAD).

What do computational predictors say about ECT2 p.Arg675Gln (c.2024G>A)?

AlphaMissense predicts likely benign (score 0.1849) — an in-silico prediction, not a clinical call.

ECT2 p.Arg675Gln

c.2024G>A · rs146823982 · VCV2300889

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1849 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0331%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1849	likely benign
REVEL	0.211	benign-leaning
SaProt	LLR -12.48	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
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	24.8	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 0.0331% Middle Eastern · 2/6,048 alleles

Filtering AF 0.00583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00236% 38/1,612,968 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0331%	3,024
Remaining individualsnot grpmax-eligible	0.00641%	15,607
South Asian	0.00439%	22,758
African / African-American	0.00267%	37,415
European (non-Finnish)	0.0022%	45,365

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.Arg675Gln
Coding: c.2024G>A
MANE Select: NM_001258315
dbSNP: rs146823982
Type: single nucleotide variant
Location: chr3:172802898 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.17 · 3 PDB
Residue 675: a β-strand; the ph domain

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

Similar variants

ECT2 p.Arg675Trp Uncertain significance ★ ⚠ same residue
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

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-arg675gln (accessed [today's date]).

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