Is ECT2L p.Arg296Pro (c.887G>C) pathogenic?

ECT2L p.Arg296Pro (c.887G>C) is classified Uncertain significance in ECT2L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). AlphaMissense: likely pathogenic (0.8592); Very rare (popmax 8.51e-05%, nfe).

How common is ECT2L p.Arg296Pro (c.887G>C) in the general population?

ECT2L p.Arg296Pro (c.887G>C) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

What do computational predictors say about ECT2L p.Arg296Pro (c.887G>C)?

AlphaMissense predicts likely pathogenic (score 0.8592) — an in-silico prediction, not a clinical call.

ECT2L p.Arg296Pro

c.887G>C · VCV3506586

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8592 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8592	likely pathogenic · top 5% in ECT2L
REVEL	0.429	indeterminate
SaProt	LLR -11.19	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.24	donor loss · deltas
Pangolin	Δ0.26	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	21.1	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 8.51e-05% European (non-Finnish) · 1/1,174,924 alleles

Overall 6.9e-05% 1/1,449,282 alleles · very rare

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.Arg296Pro
Coding: c.887G>C
MANE Select: NM_001077706
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.Arg296Gln 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-arg296pro (accessed [today's date]).

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