Is EEF2 p.Ala338Gly (c.1013C>G) pathogenic?

EEF2 p.Ala338Gly (c.1013C>G) is classified Uncertain significance in EEF2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-24). AlphaMissense: ambiguous (0.3879); Very rare (popmax 0.000518%, nfe).

How common is EEF2 p.Ala338Gly (c.1013C>G) in the general population?

EEF2 p.Ala338Gly (c.1013C>G) is very rare (popmax 0.000518%, nfe) (gnomAD).

What do computational predictors say about EEF2 p.Ala338Gly (c.1013C>G)?

AlphaMissense predicts ambiguous (score 0.3879) — an in-silico prediction, not a clinical call.

EEF2 p.Ala338Gly

c.1013C>G · VCV3274552

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3879 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000518%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3879	ambiguous
REVEL	0.207	benign-leaning
SaProt	LLR -10.35	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 1,418 bp · p 0.16 · 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 0.000518% European (non-Finnish) · 6/1,159,140 alleles

Filtering AF 0.000186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000122%

Overall 0.000382% 6/1,569,742 alleles · very rare

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.Ala338Gly
Coding: c.1013C>G
MANE Select: NM_001961
Type: single nucleotide variant
Location: chr19:3980978 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 26 PDB
Residue 338: 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.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
EEF2 p.Asn673Ser 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-ala338gly (accessed [today's date]).

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