Is ECT2L p.Cys645Phe (c.1934G>T) pathogenic?

ECT2L p.Cys645Phe (c.1934G>T) is classified Uncertain significance in ECT2L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-11). AlphaMissense: likely benign (0.2889); Ultra-rare (popmax 0.0245%, nfe).

How common is ECT2L p.Cys645Phe (c.1934G>T) in the general population?

ECT2L p.Cys645Phe (c.1934G>T) is ultra-rare (popmax 0.0245%, nfe) (gnomAD).

What do computational predictors say about ECT2L p.Cys645Phe (c.1934G>T)?

AlphaMissense predicts likely benign (score 0.2889) — an in-silico prediction, not a clinical call.

ECT2L p.Cys645Phe

c.1934G>T · rs373301762 · VCV3087103

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2889 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2889	likely benign
REVEL	0.29	benign-leaning
SaProt	LLR -10.81	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 8.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 89 kb · p 0.11 · regional, not allelic
Overall
CADD	24.0	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 0.0245% European (non-Finnish) · 289/1,180,040 alleles

Filtering AF 0.0221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0212%

Overall 0.0187% 302/1,614,110 alleles · ultra-rare exomes 290/1,461,874 · genomes 12/152,236 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0245%	4,083
Remaining individualsnot grpmax-eligible	0.0144%	6,943
African / African-American	0.004%	24,981
Admixed American	0.00167%	60,006

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.Cys645Phe
Coding: c.1934G>T
MANE Select: NM_001077706
dbSNP: rs373301762
Type: single nucleotide variant
Location: chr6:138882777 (GRCh38)
Gene constraint: LOEUF 1.127 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.75 · 1 PDB
Residue 645: the dh domain

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-cys645phe (accessed [today's date]).

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