Is ECT2L p.Arg287Trp (c.859C>T) pathogenic?

ECT2L p.Arg287Trp (c.859C>T) is classified Uncertain significance in ECT2L (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: likely benign (0.0923); Ultra-rare (popmax 0.0165%, mid).

How common is ECT2L p.Arg287Trp (c.859C>T) in the general population?

ECT2L p.Arg287Trp (c.859C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about ECT2L p.Arg287Trp (c.859C>T)?

AlphaMissense predicts likely benign (score 0.0923) — an in-silico prediction, not a clinical call.

ECT2L p.Arg287Trp

c.859C>T · rs200093583 · VCV3087110

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0923 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0923	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -8.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.43	donor loss · deltas
Pangolin	Δ0.26	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1	GERP 0.6
Regional constraint	o/e 0.95	unconstrained · MANE · 89 kb · p 0.11 · regional, not allelic
Overall
CADD	19.42	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 0.0165% Middle Eastern · 1/6,074 alleles

Filtering AF 0.00758% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00707%

Overall 0.0101% 162/1,610,386 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.115%	866
Middle Easterngrpmax	0.0165%	6,074
South Asian	0.0122%	8,211
Remaining individualsnot grpmax-eligible	0.00963%	10,386
European (non-Finnish)	0.009%	11,117
Admixed American	0.00336%	29,758
African / African-American	0.00268%	37,344

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg287Trp
Coding: c.859C>T
MANE Select: NM_001077706
dbSNP: rs200093583
Type: single nucleotide variant
Location: chr6:138846633 (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.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
ECT2L p.Ala605Gly 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-arg287trp (accessed [today's date]).

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