Is EEF1A2 p.Thr239Arg (c.716C>G) pathogenic?

EEF1A2 p.Thr239Arg (c.716C>G) is classified Uncertain significance in EEF1A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-09). AlphaMissense: ambiguous (0.5365); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 33.

What condition is associated with EEF1A2 p.Thr239Arg (c.716C>G)?

EEF1A2 p.Thr239Arg (c.716C>G) is associated with developmental and epileptic encephalopathy, 33 (ClinVar).

How common is EEF1A2 p.Thr239Arg (c.716C>G) in the general population?

EEF1A2 p.Thr239Arg (c.716C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EEF1A2 p.Thr239Arg (c.716C>G)?

AlphaMissense predicts ambiguous (score 0.5365) — an in-silico prediction, not a clinical call.

EEF1A2 p.Thr239Arg

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.716C>G · rs993963334 · VCV1470375

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5365 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

developmental and epileptic encephalopathy, 33

Computational evidence

Protein change
AlphaMissense	0.5365	ambiguous
REVEL	0.108	moderately benign-leaning
SaProt	LLR -10.93	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 4,822 bp · p 4e-36 · regional, not allelic
Overall
CADD	23.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EEF1A2
Protein: p.Thr239Arg
Coding: c.716C>G
MANE Select: NM_001958
dbSNP: rs993963334
Type: single nucleotide variant
Location: chr20:63493193 (GRCh38)
Gene constraint: LOEUF 0.314 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.70 · 2 PDB
Residue 239: the tr-type g domain; a modified residue (phosphothreonine)

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.Thr239= Likely benign ★★ same residue
EEF1A2 p.Thr239Met Conflicting classifications of pathogenicity ★ ⚠ 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-thr239arg (accessed [today's date]).

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