Is EEF2 p.Met340Val (c.1018A>G) pathogenic?

EEF2 p.Met340Val (c.1018A>G) is classified Uncertain significance in EEF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-13). AlphaMissense: likely pathogenic (0.8607); Absent from gnomAD v4.1.

How common is EEF2 p.Met340Val (c.1018A>G) in the general population?

EEF2 p.Met340Val (c.1018A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EEF2 p.Met340Val (c.1018A>G)?

AlphaMissense predicts likely pathogenic (score 0.8607) — an in-silico prediction, not a clinical call.

EEF2 p.Met340Val

c.1018A>G · rs2512203158 · VCV1710663

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8607 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,572,362)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8607	likely pathogenic
REVEL	0.432	indeterminate
SaProt	LLR -10.30	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 1,418 bp · p 0.16 · regional, not allelic
Overall
CADD	25.0	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

No allele count reported in gnomAD v4.1 (AN 1,572,362). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EEF2
Protein: p.Met340Val
Coding: c.1018A>G
MANE Select: NM_001961
dbSNP: rs2512203158
Type: single nucleotide variant
Location: chr19:3980973 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 26 PDB
Residue 340: the tr-type g domain; an α-helix

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

Similar variants

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
EEF2 p.Arg726Trp 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-met340val (accessed [today's date]).

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