Is EEF2 p.Ile385Val (c.1153A>G) pathogenic?

EEF2 p.Ile385Val (c.1153A>G) is classified Uncertain significance in EEF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: likely benign (0.1253); Very rare (popmax 0.00892%, eas).

How common is EEF2 p.Ile385Val (c.1153A>G) in the general population?

EEF2 p.Ile385Val (c.1153A>G) is very rare (popmax 0.00892%, eas) (gnomAD).

What do computational predictors say about EEF2 p.Ile385Val (c.1153A>G)?

AlphaMissense predicts likely benign (score 0.1253) — an in-silico prediction, not a clinical call.

EEF2 p.Ile385Val

c.1153A>G · rs1311584123 · VCV3087294

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1253 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1253	likely benign
REVEL	0.121	moderately benign-leaning
SaProt	LLR -10.20	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 871 bp · p 0.00092 · regional, not allelic
Overall
CADD	22.4	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 0.00892% East Asian · 4/44,854 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000248% 4/1,612,968 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.Ile385Val
Coding: c.1153A>G
MANE Select: NM_001961
dbSNP: rs1311584123
Type: single nucleotide variant
Location: chr19:3980707 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 26 PDB
Residue 385: 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-ile385val (accessed [today's date]).

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