Is EEF1A2 p.Met429Val (c.1285A>G) pathogenic?

EEF1A2 p.Met429Val (c.1285A>G) is classified Uncertain significance in EEF1A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: likely pathogenic (0.9777); Very rare (popmax 0.00306%, eas); Associated with developmental and epileptic encephalopathy, 33.

What condition is associated with EEF1A2 p.Met429Val (c.1285A>G)?

EEF1A2 p.Met429Val (c.1285A>G) is associated with developmental and epileptic encephalopathy, 33 (ClinVar).

How common is EEF1A2 p.Met429Val (c.1285A>G) in the general population?

EEF1A2 p.Met429Val (c.1285A>G) is very rare (popmax 0.00306%, eas) (gnomAD).

What do computational predictors say about EEF1A2 p.Met429Val (c.1285A>G)?

AlphaMissense predicts likely pathogenic (score 0.9777) — an in-silico prediction, not a clinical call.

EEF1A2 p.Met429Val

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.1285A>G · rs1211620501 · VCV2999464

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9777 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00306%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

developmental and epileptic encephalopathy, 33

Computational evidence

Protein change
AlphaMissense	0.9777	likely pathogenic
REVEL	0.3	indeterminate
SaProt	LLR -14.12	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 5.9	GERP 0.92, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 108 bp · p 0.00057 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00306% East Asian · 1/32,704 alleles

Filtering AF 3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000229% 3/1,312,776 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00306%	32,704
European (non-Finnish)	0.00018%	554,388

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.Met429Val
Coding: c.1285A>G
MANE Select: NM_001958
dbSNP: rs1211620501
Type: single nucleotide variant
Location: chr20:63488405 (GRCh38)
Gene constraint: LOEUF 0.314 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.70 · 2 PDB

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.Met429Arg Uncertain significance ★★ ⚠ 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
EEF1A2 p.Glu124Lys 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-met429val (accessed [today's date]).

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