Is EEF1A2 p.Gly14Ser (c.40G>A) pathogenic?

EEF1A2 p.Gly14Ser (c.40G>A) is classified Uncertain significance in EEF1A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-15). AlphaMissense: likely pathogenic (0.9996); Ultra-rare (popmax 0.0165%, mid); Associated with developmental and epileptic encephalopathy, 33.

What condition is associated with EEF1A2 p.Gly14Ser (c.40G>A)?

EEF1A2 p.Gly14Ser (c.40G>A) is associated with developmental and epileptic encephalopathy, 33 (ClinVar).

How common is EEF1A2 p.Gly14Ser (c.40G>A) in the general population?

EEF1A2 p.Gly14Ser (c.40G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about EEF1A2 p.Gly14Ser (c.40G>A)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

EEF1A2 p.Gly14Ser

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.40G>A · rs750037735 · VCV581903

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 33

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic
REVEL	0.833	moderately pathogenic-leaning
SaProt	LLR -15.48	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.18	constrained · MANE · 2,668 bp · p 1.1e-24 · regional, not allelic
Overall
CADD	29.6	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 0.0165% Middle Eastern · 1/6,058 alleles

Overall 6.85e-05% 1/1,460,752 alleles · ultra-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.Gly14Ser
Coding: c.40G>A
MANE Select: NM_001958
dbSNP: rs750037735
Type: single nucleotide variant
Location: chr20:63497724 (GRCh38)
Gene constraint: LOEUF 0.314 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.70 · 2 PDB
Residue 14: the tr-type g domain; the 'g1' region

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.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
EEF1A2 p.Gly384Arg 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-gly14ser (accessed [today's date]).

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