Is ECT2 p.Met368Val (c.1102A>G) pathogenic?

ECT2 p.Met368Val (c.1102A>G) is classified Uncertain significance in ECT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-17). AlphaMissense: likely benign (0.0609); Ultra-rare (popmax 0.0233%, amr).

How common is ECT2 p.Met368Val (c.1102A>G) in the general population?

ECT2 p.Met368Val (c.1102A>G) is ultra-rare (popmax 0.0233%, amr) (gnomAD).

What do computational predictors say about ECT2 p.Met368Val (c.1102A>G)?

AlphaMissense predicts likely benign (score 0.0609) — an in-silico prediction, not a clinical call.

ECT2 p.Met368Val

c.1102A>G · rs369761944 · VCV2556460

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0609 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0609	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -6.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.29	GERP -1.3, phastCons 0.048
Regional constraint	o/e 0.87	unconstrained · MANE · 66 kb · p 1.6e-05 · regional, not allelic
Overall
CADD	18.89	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 0.0233% Admixed American · 14/60,004 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.0083% 134/1,614,014 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0233%	4,286
African / African-American	0.00934%	10,702
European (non-Finnish)	0.00873%	11,456
South Asian	0.00659%	15,181
Remaining individualsnot grpmax-eligible	0.0048%	20,828
East Asian	0.00223%	44,896

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.Met368Val
Coding: c.1102A>G
MANE Select: NM_001258315
dbSNP: rs369761944
Type: single nucleotide variant
Location: chr3:172764311 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.17 · 3 PDB

Full ECT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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
ECT2 p.Arg194Met 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-met368val (accessed [today's date]).

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