Is ECT2 p.Arg675Trp (c.2023C>T) pathogenic?

ECT2 p.Arg675Trp (c.2023C>T) is classified Uncertain significance in ECT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-26). AlphaMissense: likely pathogenic (0.6046); Very rare (popmax 0.00668%, afr).

How common is ECT2 p.Arg675Trp (c.2023C>T) in the general population?

ECT2 p.Arg675Trp (c.2023C>T) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about ECT2 p.Arg675Trp (c.2023C>T)?

AlphaMissense predicts likely pathogenic (score 0.6046) — an in-silico prediction, not a clinical call.

ECT2 p.Arg675Trp

c.2023C>T · rs1365878389 · VCV2551982

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6046 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6046	likely pathogenic
REVEL	0.333	indeterminate
SaProt	LLR -16.24	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.32	acceptor loss, 36 bp away · masked 0 · deltas
Pangolin	Δ0.33	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.57	GERP 1.1, phastCons 0.039
Regional constraint	o/e 0.87	unconstrained · MANE · 66 kb · p 1.6e-05 · regional, not allelic
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00668% African / African-American · 5/74,868 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00112% 18/1,612,918 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,974
East Asian	0.00223%	44,754
South Asian	0.0011%	91,036
European (non-Finnish)	0.000933%	107,217

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.Arg675Trp
Coding: c.2023C>T
MANE Select: NM_001258315
dbSNP: rs1365878389
Type: single nucleotide variant
Location: chr3:172802897 (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.Arg675Gln 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-arg675trp (accessed [today's date]).

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