Is EEF1A2 p.Val226Leu (c.676G>C) pathogenic?

EEF1A2 p.Val226Leu (c.676G>C) is classified Uncertain significance in EEF1A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). AlphaMissense: likely benign (0.1035); Very rare (popmax 0.000175%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EEF1A2 p.Val226Leu (c.676G>C)?

EEF1A2 p.Val226Leu (c.676G>C) is associated with Inborn genetic diseases (ClinVar).

How common is EEF1A2 p.Val226Leu (c.676G>C) in the general population?

EEF1A2 p.Val226Leu (c.676G>C) is very rare (popmax 0.000175%, nfe) (gnomAD).

What do computational predictors say about EEF1A2 p.Val226Leu (c.676G>C)?

AlphaMissense predicts likely benign (score 0.1035) — an in-silico prediction, not a clinical call.

EEF1A2 p.Val226Leu

c.676G>C · rs1437591277 · VCV2612230

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1035 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000175%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1035	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -7.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -3.8, phastCons 0.98
Regional constraint	o/e 0.46	unconstrained · MANE · 1,861 bp · p 1.2e-12 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.000175% European (non-Finnish) · 2/1,144,600 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000143% 2/1,394,662 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: EEF1A2
Protein: p.Val226Leu
Coding: c.676G>C
MANE Select: NM_001958
dbSNP: rs1437591277
Type: single nucleotide variant
Location: chr20:63493233 (GRCh38)
Gene constraint: LOEUF 0.314 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.70 · 2 PDB
Residue 226: the tr-type g domain; a β-strand

Full EEF1A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EEF1A2 p.Val226Met Uncertain significance ★★ ⚠ same residue
EEF1A2 p.Ala117Val Uncertain significance ★★ ⚠ same condition
EEF1A2 p.Arg247Cys Uncertain significance ★★ ⚠ same condition
EEF1A2 p.Gly397Glu Uncertain significance ★★ ⚠ same condition
EEF1A2 p.Lys179Arg Uncertain significance ★★ ⚠ same condition
EEF1A2 p.Val150Met Uncertain significance ★★ ⚠ same condition
EEF1A2 p.Ala117= Benign/Likely benign ★★ same condition
EEF1A2 p.Ala125= Benign/Likely benign ★★ same condition

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/eef1a2-p-val226leu (accessed [today's date]).

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