Is EEF1A2 p.Arg247Cys (c.739C>T) pathogenic?

EEF1A2 p.Arg247Cys (c.739C>T) is classified Uncertain significance in EEF1A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-09). AlphaMissense: likely pathogenic (0.9898); Very rare (popmax 0.000175%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EEF1A2 p.Arg247Cys (c.739C>T)?

EEF1A2 p.Arg247Cys (c.739C>T) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 33 (ClinVar).

How common is EEF1A2 p.Arg247Cys (c.739C>T) in the general population?

EEF1A2 p.Arg247Cys (c.739C>T) is very rare (popmax 0.000175%, nfe) (gnomAD).

What do computational predictors say about EEF1A2 p.Arg247Cys (c.739C>T)?

AlphaMissense predicts likely pathogenic (score 0.9898) — an in-silico prediction, not a clinical call.

EEF1A2 p.Arg247Cys

c.739C>T · rs1325353717 · VCV589089

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9898 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000175%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9898	likely pathogenic
REVEL	0.458	indeterminate
SaProt	LLR -13.32	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 4,822 bp · p 4e-36 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.000175% European (non-Finnish) · 2/1,145,922 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000143% 2/1,396,406 alleles · very rare

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.Arg247Cys
Coding: c.739C>T
MANE Select: NM_001958
dbSNP: rs1325353717
Type: single nucleotide variant
Location: chr20:63493170 (GRCh38)
Gene constraint: LOEUF 0.314 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.70 · 2 PDB
Residue 247: a β-strand

Full EEF1A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 33

Similar variants

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
EEF1A2 p.Gly384Arg 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-arg247cys (accessed [today's date]).

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