Is EEF2 p.Glu80Lys (c.238G>A) pathogenic?

EEF2 p.Glu80Lys (c.238G>A) is classified Uncertain significance in EEF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-30). AlphaMissense: ambiguous (0.4302); Very rare (popmax 0.00223%, eas).

How common is EEF2 p.Glu80Lys (c.238G>A) in the general population?

EEF2 p.Glu80Lys (c.238G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about EEF2 p.Glu80Lys (c.238G>A)?

AlphaMissense predicts ambiguous (score 0.4302) — an in-silico prediction, not a clinical call.

EEF2 p.Glu80Lys

c.238G>A · rs35967493 · VCV2581454

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4302 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
AlphaMissense	0.4302	ambiguous
REVEL	0.389	indeterminate
SaProt	LLR -10.66	damaging
Splicing
SpliceAI	Δ0.65	acceptor gain · deltas
Pangolin	Δ0.32	gain · loss 0.08 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.24	unconstrained · MANE · 56 bp · p 0.22 · regional, not allelic
Overall
CADD	34.0	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 0.00223% East Asian · 1/44,838 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000342% 5/1,461,496 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,838
European (non-Finnish)	0.000339%	294,949

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.Glu80Lys
Coding: c.238G>A
MANE Select: NM_001961
dbSNP: rs35967493
Type: single nucleotide variant
Location: chr19:3983272 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 26 PDB
Residue 80: the tr-type g domain; a β-strand

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-glu80lys (accessed [today's date]).

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