Is EEF2 p.Pro596His (c.1787C>A) pathogenic?

EEF2 p.Pro596His (c.1787C>A) is classified Pathogenic in EEF2 (ClinVar, Single submitter, 2 submitters; last evaluated 2019-12-06). AlphaMissense: likely pathogenic (0.9984); Absent from gnomAD v4.1; Associated with spinocerebellar ataxia type 26.

What condition is associated with EEF2 p.Pro596His (c.1787C>A)?

EEF2 p.Pro596His (c.1787C>A) is associated with spinocerebellar ataxia type 26 (ClinVar).

How common is EEF2 p.Pro596His (c.1787C>A) in the general population?

EEF2 p.Pro596His (c.1787C>A) is absent from gnomAD v4.1 (gnomAD).

How is Spinocerebellar ataxia type 26 inherited?

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

What do computational predictors say about EEF2 p.Pro596His (c.1787C>A)?

AlphaMissense predicts likely pathogenic (score 0.9984) — an in-silico prediction, not a clinical call.

EEF2 p.Pro596His

c.1787C>A · rs587777052 · VCV66077

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9984 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,534,282)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

spinocerebellar ataxia type 26

Computational evidence

Protein change
AlphaMissense	0.9984	likely pathogenic ✓ concordant with ClinVar
REVEL	0.536	indeterminate
SaProt	LLR -17.44	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 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 1,578 bp · p 7.1e-09 · regional, not allelic
Overall
CADD	32.0	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 1,534,282). 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: EEF2
Protein: p.Pro596His
Coding: c.1787C>A
MANE Select: NM_001961
dbSNP: rs587777052
Type: single nucleotide variant
Location: chr19:3978099 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 26 PDB
Residue 596: a UniProt-annotated variant site (in sca26; compromises the mechanics of translocation)

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 c.1150+15T>C Benign ★★ same condition
EEF2 p.His544= Benign ★★ 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
EEF2 p.Met494Leu Uncertain significance ★ ⚠ same condition
EEF2 p.Pro377Leu 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-pro596his (accessed [today's date]).

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