Is EEF2 p.Asp295Val (c.884A>T) pathogenic?

EEF2 p.Asp295Val (c.884A>T) is classified Uncertain significance in EEF2 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.8538); Very rare (popmax 0.0011%, sas); Associated with spinocerebellar ataxia type 19/22.

What condition is associated with EEF2 p.Asp295Val (c.884A>T)?

EEF2 p.Asp295Val (c.884A>T) is associated with spinocerebellar ataxia type 19/22 (ClinVar).

How common is EEF2 p.Asp295Val (c.884A>T) in the general population?

EEF2 p.Asp295Val (c.884A>T) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Spinocerebellar ataxia type 19/22 inherited?

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

What do computational predictors say about EEF2 p.Asp295Val (c.884A>T)?

AlphaMissense predicts likely pathogenic (score 0.8538) — an in-silico prediction, not a clinical call.

EEF2 p.Asp295Val

c.884A>T · rs1231921301 · VCV2627477

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8538 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

spinocerebellar ataxia type 19/22

Computational evidence

Protein change
AlphaMissense	0.8538	likely pathogenic
REVEL	0.915	moderately pathogenic-leaning
SaProt	LLR -10.85	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 1,418 bp · p 0.16 · regional, not allelic
Overall
CADD	29.3	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 0.0011% South Asian · 1/91,052 alleles

Overall 0.000137% 2/1,461,556 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,472
South Asiangrpmax	0.0011%	91,052

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp295Val
Coding: c.884A>T
MANE Select: NM_001961
dbSNP: rs1231921301
Type: single nucleotide variant
Location: chr19:3981960 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 26 PDB
Residue 295: the tr-type g domain; an α-helix

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

Disease context

spinocerebellar ataxia type 19/22 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Spinocerebellar ataxia type 19/22 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

EEF2 p.Asp295Gly Uncertain significance ★ ⚠ same residue
EEF2 p.Ala237Thr Uncertain significance ★★ ⚠ same type
EEF2 p.Ala238Thr Uncertain significance ★★ ⚠ same type
EEF2 p.Ala338Gly Uncertain significance ★★ ⚠ same type
EEF2 p.Ala624Thr Uncertain significance ★★ ⚠ same type
EEF2 p.Ala808Val Uncertain significance ★★ ⚠ same type
EEF2 p.Arg633His Uncertain significance ★★ ⚠ same type
EEF2 p.Arg647His Uncertain significance ★★ ⚠ same type

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-asp295val (accessed [today's date]).

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