Is EEF1A2 p.Val253= (c.759G>A) pathogenic?

EEF1A2 p.Val253= (c.759G>A) is classified Likely benign in EEF1A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-13). Very rare (popmax 0.00393%, amr); Associated with developmental and epileptic encephalopathy, 33.

What condition is associated with EEF1A2 p.Val253= (c.759G>A)?

EEF1A2 p.Val253= (c.759G>A) is associated with developmental and epileptic encephalopathy, 33 (ClinVar).

How common is EEF1A2 p.Val253= (c.759G>A) in the general population?

EEF1A2 p.Val253= (c.759G>A) is very rare (popmax 0.00393%, amr) (gnomAD).

EEF1A2 p.Val253=

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.759G>A · rs372796244 · VCV2731511

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00393%, 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 -0.33	GERP -3.8, phastCons 0.11
Overall
CADD	2.617	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00393% Admixed American · 2/50,860 alleles

Filtering AF 0.000652% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000244%

Overall 0.000258% 4/1,548,270 alleles · very rare exomes 3/1,396,198 · genomes 1/152,072 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00393%	25,430
European (non-Finnish)	0.000175%	572,941

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.Val253=
Coding: c.759G>A
MANE Select: NM_001958
dbSNP: rs372796244
Type: single nucleotide variant
Location: chr20:63493150 (GRCh38)
Gene constraint: LOEUF 0.314 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.70 · 2 PDB
Residue 253: 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.Val253Met 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-val253 (accessed [today's date]).

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