Is EEF1A2 p.Ile320Val (c.958A>G) pathogenic?

EEF1A2 p.Ile320Val (c.958A>G) is classified Uncertain significance in EEF1A2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-10). AlphaMissense: likely benign (0.1376); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 33.

What condition is associated with EEF1A2 p.Ile320Val (c.958A>G)?

EEF1A2 p.Ile320Val (c.958A>G) is associated with developmental and epileptic encephalopathy, 33, intellectual disability, autosomal dominant 38 (ClinVar).

How common is EEF1A2 p.Ile320Val (c.958A>G) in the general population?

EEF1A2 p.Ile320Val (c.958A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EEF1A2 p.Ile320Val (c.958A>G)?

AlphaMissense predicts likely benign (score 0.1376) — an in-silico prediction, not a clinical call.

EEF1A2 p.Ile320Val

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.958A>G · rs935904739 · VCV2431392

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1376 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 33

Computational evidence

Protein change
AlphaMissense	0.1376	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -7.75	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 2.4	GERP 0.088, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 4,822 bp · p 4e-36 · regional, not allelic
Overall
CADD	17.89	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

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.Ile320Val
Coding: c.958A>G
MANE Select: NM_001958
dbSNP: rs935904739
Type: single nucleotide variant
Location: chr20:63490550 (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

Also linked: intellectual disability, autosomal dominant 38

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

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

Similar variants

EEF1A2 p.Ile320Leu Uncertain significance ★ ⚠ same residue
EEF1A2 p.Ile320Thr Uncertain significance ★ ⚠ same residue
EEF1A2 p.Arg266Gln Likely pathogenic ★★ same condition
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

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-ile320val (accessed [today's date]).

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