Is EEF2 p.Val747= (c.2241G>A) pathogenic?

EEF2 p.Val747= (c.2241G>A) is classified Conflicting classifications of pathogenicity in EEF2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-08-24). Ultra-rare (popmax 0.0168%, mid); Associated with spinocerebellar ataxia type 26.

What condition is associated with EEF2 p.Val747= (c.2241G>A)?

EEF2 p.Val747= (c.2241G>A) is associated with spinocerebellar ataxia type 26 (ClinVar).

How common is EEF2 p.Val747= (c.2241G>A) in the general population?

EEF2 p.Val747= (c.2241G>A) is ultra-rare (popmax 0.0168%, mid) (gnomAD).

How is Spinocerebellar ataxia type 26 inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

EEF2 p.Val747=

c.2241G>A · rs772173797 · VCV585829

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, mid)

Conditions

spinocerebellar ataxia type 26

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 0.23	GERP 1.1, phastCons 0.97
Overall
CADD	7.581	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0168% Middle Eastern · 1/5,956 alleles

Filtering AF 0.00259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.00284% 45/1,584,842 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0168%	5,956
Admixed American	0.00523%	19,131
European (non-Finnish)	0.00343%	29,151
Remaining individualsnot grpmax-eligible	0.00163%	61,286

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: EEF2
Protein: p.Val747=
Coding: c.2241G>A
MANE Select: NM_001961
dbSNP: rs772173797
Type: single nucleotide variant
Location: chr19:3977437 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 26 PDB
Residue 747: a β-strand

Full EEF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spinocerebellar ataxia type 26 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Spinocerebellar ataxia type 26 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

EEF2 p.Val747Met Uncertain significance ★★ ⚠ same residue
EEF2 c.1150+15T>C Benign ★★ same condition
EEF2 p.His544= Benign ★★ same condition
EEF2 p.Pro596His Pathogenic ★ same condition
EEF2 p.Asn600Lys Uncertain significance ★ ⚠ same condition
EEF2 p.Asn660Ser Uncertain significance ★ same condition
EEF2 p.Leu155Met Uncertain significance ★ same condition
EEF2 p.Met453Ile Uncertain significance ★ ⚠ 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/eef2-p-val747 (accessed [today's date]).

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