Is EEF1A2 p.Arg423Cys (c.1267C>T) pathogenic?

EEF1A2 p.Arg423Cys (c.1267C>T) is classified Pathogenic/Likely pathogenic in EEF1A2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2022-09-07). AlphaMissense: likely pathogenic (0.9994); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 33.

What condition is associated with EEF1A2 p.Arg423Cys (c.1267C>T)?

EEF1A2 p.Arg423Cys (c.1267C>T) is associated with developmental and epileptic encephalopathy, 33 (ClinVar).

How common is EEF1A2 p.Arg423Cys (c.1267C>T) in the general population?

EEF1A2 p.Arg423Cys (c.1267C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EEF1A2 p.Arg423Cys (c.1267C>T)?

AlphaMissense predicts likely pathogenic (score 0.9994) — an in-silico prediction, not a clinical call.

EEF1A2 p.Arg423Cys

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.1267C>T · rs886039346 · VCV265111

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9994 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,451,526)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

developmental and epileptic encephalopathy, 33

Computational evidence

Protein change
AlphaMissense	0.9994	likely pathogenic ✓ concordant with ClinVar
REVEL	0.318	indeterminate
SaProt	LLR -14.44	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.83 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 0.64, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 4,822 bp · p 4e-36 · regional, not allelic
Overall
CADD	27.7	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

No allele count reported in gnomAD v4.1 (AN 1,451,526). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EEF1A2
Protein: p.Arg423Cys
Coding: c.1267C>T
MANE Select: NM_001958
dbSNP: rs886039346
Type: single nucleotide variant
Location: chr20:63488423 (GRCh38)
Gene constraint: LOEUF 0.314 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.70 · 2 PDB
Residue 423: 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.Arg423= Likely benign ★★ same residue
EEF1A2 p.Arg423Gln Uncertain significance ★ same residue
EEF1A2 p.Arg266Trp 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-arg423cys (accessed [today's date]).

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