Is EEF2 p.Thr363Met (c.1088C>T) pathogenic?

EEF2 p.Thr363Met (c.1088C>T) is classified Uncertain significance in EEF2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-30). AlphaMissense: likely benign (0.2286); Very rare (popmax 0.00294%, nfe).

How common is EEF2 p.Thr363Met (c.1088C>T) in the general population?

EEF2 p.Thr363Met (c.1088C>T) is very rare (popmax 0.00294%, nfe) (gnomAD).

What do computational predictors say about EEF2 p.Thr363Met (c.1088C>T)?

AlphaMissense predicts likely benign (score 0.2286) — an in-silico prediction, not a clinical call.

EEF2 p.Thr363Met

c.1088C>T · rs980260154 · VCV447289

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2286 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00294%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2286	likely benign
REVEL	0.308	indeterminate
SaProt	LLR -11.06	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 871 bp · p 0.00092 · regional, not allelic
Overall
CADD	31.0	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 0.00294% European (non-Finnish) · 34/1,156,548 alleles

Filtering AF 0.00212% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00187%

Overall 0.00236% 37/1,565,768 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00294%	34,016
East Asian	0.00236%	42,286
Finnishnot grpmax-eligible	0.00172%	58,078
African / African-American	0.00135%	73,826

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: EEF2
Protein: p.Thr363Met
Coding: c.1088C>T
MANE Select: NM_001961
dbSNP: rs980260154
Type: single nucleotide variant
Location: chr19:3980903 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 26 PDB
Residue 363: an α-helix

Full EEF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EEF2 p.Thr363= Likely benign ★ same residue
EEF2 p.Ala237Thr Uncertain significance ★★ ⚠ same type
EEF2 p.Ala238Thr Uncertain significance ★★ ⚠ same type
EEF2 p.Ala338Gly Uncertain significance ★★ ⚠ same type
EEF2 p.Ala624Thr Uncertain significance ★★ ⚠ same type
EEF2 p.Ala808Val Uncertain significance ★★ ⚠ same type
EEF2 p.Arg633His Uncertain significance ★★ ⚠ same type
EEF2 p.Arg647His 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/eef2-p-thr363met (accessed [today's date]).

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