Is EEF1A2 p.Val437Phe (c.1309G>T) pathogenic?

EEF1A2 p.Val437Phe (c.1309G>T) is classified Likely pathogenic in EEF1A2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2022-01-27). AlphaMissense: likely pathogenic (0.9856); Very rare (popmax 7.53e-05%); Associated with developmental and epileptic encephalopathy, 33.

What condition is associated with EEF1A2 p.Val437Phe (c.1309G>T)?

EEF1A2 p.Val437Phe (c.1309G>T) is associated with developmental and epileptic encephalopathy, 33 (ClinVar).

How common is EEF1A2 p.Val437Phe (c.1309G>T) in the general population?

EEF1A2 p.Val437Phe (c.1309G>T) is very rare (popmax 7.53e-05%) (gnomAD).

What do computational predictors say about EEF1A2 p.Val437Phe (c.1309G>T)?

AlphaMissense predicts likely pathogenic (score 0.9856) — an in-silico prediction, not a clinical call.

EEF1A2 p.Val437Phe

Q: How is Non-specific early-onset epileptic encephalopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1309G>T · rs1057521655 · VCV383531

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9856 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 7.53e-05%)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

developmental and epileptic encephalopathy, 33

Computational evidence

Protein change
AlphaMissense	0.9856	likely pathogenic ✓ concordant with ClinVar
REVEL	0.417	indeterminate
SaProt	LLR -14.45	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 5.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 108 bp · p 0.00057 · regional, not allelic
Overall
CADD	26.6	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 7.53e-05%

Overall 7.53e-05% 1/1,328,124 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.Val437Phe
Coding: c.1309G>T
MANE Select: NM_001958
dbSNP: rs1057521655
Type: single nucleotide variant
Location: chr20:63488381 (GRCh38)
Gene constraint: LOEUF 0.314 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.70 · 2 PDB
Residue 437: a β-strand

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

Disease context

developmental and epileptic encephalopathy, 33 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Non-specific early-onset epileptic encephalopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Infancy, Neonatal

Similar variants

EEF1A2 p.Val437Ile Uncertain significance ★★ ⚠ same residue
EEF1A2 p.Val437= Likely benign ★ same residue
EEF1A2 p.Arg266Trp Pathogenic/Likely pathogenic ★★ same condition
EEF1A2 p.Arg423Cys Pathogenic/Likely pathogenic ★★ same condition
EEF1A2 p.Arg69Cys Pathogenic ★★ same condition
EEF1A2 p.Asp91Asn Pathogenic ★★ same condition
EEF1A2 p.Asp97Asn Pathogenic/Likely pathogenic ★★ same condition
EEF1A2 p.Glu122Lys Pathogenic/Likely pathogenic ★★ 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-val437phe (accessed [today's date]).

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