Is ECT2L p.Arg296Gln (c.887G>A) pathogenic?

ECT2L p.Arg296Gln (c.887G>A) is classified Uncertain significance in ECT2L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). AlphaMissense: likely benign (0.1023); Ultra-rare (popmax 0.0202%, afr).

How common is ECT2L p.Arg296Gln (c.887G>A) in the general population?

ECT2L p.Arg296Gln (c.887G>A) is ultra-rare (popmax 0.0202%, afr) (gnomAD).

What do computational predictors say about ECT2L p.Arg296Gln (c.887G>A)?

AlphaMissense predicts likely benign (score 0.1023) — an in-silico prediction, not a clinical call.

ECT2L p.Arg296Gln

c.887G>A · rs780519469 · VCV2379944

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1023 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0202%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1023	likely benign
REVEL	0.375	indeterminate
SaProt	LLR -5.87	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.24	donor loss · deltas
Pangolin	Δ0.24	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.82	GERP 1.5, phastCons 0.26
Regional constraint	o/e 0.95	unconstrained · MANE · 89 kb · p 0.11 · regional, not allelic
Overall
CADD	17.86	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 0.0202% African / African-American · 15/74,190 alleles

Filtering AF 0.0124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00998%

Overall 0.00643% 103/1,601,320 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0202%	4,946
Remaining individualsnot grpmax-eligible	0.00808%	12,371
European (non-Finnish)	0.00672%	14,873
East Asian	0.00448%	22,326
Admixed American	0.00174%	57,624
South Asian	0.00113%	88,372

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: ECT2L
Protein: p.Arg296Gln
Coding: c.887G>A
MANE Select: NM_001077706
dbSNP: rs780519469
Type: single nucleotide variant
Location: chr6:138846661 (GRCh38)
Gene constraint: LOEUF 1.127 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.75 · 1 PDB

Full ECT2L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECT2L p.Arg296Pro Uncertain significance ★ ⚠ same residue
ECT2L p.Ala147Thr Uncertain significance ★ ⚠ same type
ECT2L p.Ala161Thr Uncertain significance ★ ⚠ same type
ECT2L p.Ala299Val Uncertain significance ★ ⚠ same type
ECT2L p.Ala401Ser Uncertain significance ★ ⚠ same type
ECT2L p.Ala443Ser Uncertain significance ★ ⚠ same type
ECT2L p.Ala515Gly Uncertain significance ★ ⚠ same type
ECT2L p.Ala599Thr 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/ect2l-p-arg296gln (accessed [today's date]).

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