Is EEF1A2 p.Ile368= (c.1104C>T) pathogenic?

EEF1A2 p.Ile368= (c.1104C>T) is classified Likely benign in EEF1A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-30). Very rare (popmax 0.00167%, amr); Associated with developmental and epileptic encephalopathy, 33.

What condition is associated with EEF1A2 p.Ile368= (c.1104C>T)?

EEF1A2 p.Ile368= (c.1104C>T) is associated with developmental and epileptic encephalopathy, 33 (ClinVar).

How common is EEF1A2 p.Ile368= (c.1104C>T) in the general population?

EEF1A2 p.Ile368= (c.1104C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

EEF1A2 p.Ile368=

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.1104C>T · rs965429825 · VCV1570067

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

developmental and epileptic encephalopathy, 33

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.3	GERP -3.8
Overall
CADD	1.267	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,030 alleles

Overall 0.000372% 6/1,612,794 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,240
Admixed Americangrpmax	0.00167%	60,030
African / African-American	0.00133%	75,076
South Asian	0.0011%	91,084
European (non-Finnish)	8.47e-05%	1,179,942

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile368=
Coding: c.1104C>T
MANE Select: NM_001958
dbSNP: rs965429825
Type: single nucleotide variant
Location: chr20:63489078 (GRCh38)
Gene constraint: LOEUF 0.314 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.70 · 2 PDB
Residue 368: 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.Ile368Val 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-ile368 (accessed [today's date]).

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