Is EEF2 p.His544= (c.1632T>C) pathogenic?

EEF2 p.His544= (c.1632T>C) is classified Benign in EEF2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 98.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with spinocerebellar ataxia type 26.

What condition is associated with EEF2 p.His544= (c.1632T>C)?

EEF2 p.His544= (c.1632T>C) is associated with spinocerebellar ataxia type 26 (ClinVar).

How is Spinocerebellar ataxia type 26 inherited?

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

EEF2 p.His544=

Q: How common is EEF2 p.His544= (c.1632T>C) in the general population?

EEF2 p.His544= (c.1632T>C) is common (popmax 98.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1632T>C · rs36526 · VCV128958

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 98.8%, eas) — too common for a highly-penetrant pathogenic allele

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 1.5	GERP -3.7, phastCons 1
Overall
CADD	2.938	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 98.8% East Asian · 44,335/44,858 alleles

Filtering AF 98.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 97.7%

Overall 82.1% 1,325,402/1,613,470 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	98.8%	1
African / African-American	96.5%	1
Amishnot grpmax-eligible	92.4%	1
South Asian	88.4%	1
Admixed American	88.1%	1
Remaining individualsnot grpmax-eligible	82.8%	1
Middle Eastern	80.2%	1
European (non-Finnish)	80%	1
Finnishnot grpmax-eligible	79.2%	1
Ashkenazi Jewishnot grpmax-eligible	78.2%	1

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.His544=
Coding: c.1632T>C
MANE Select: NM_001961
dbSNP: rs36526
Type: single nucleotide variant
Location: chr19:3979410 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 26 PDB
Residue 544: 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 c.1150+15T>C 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
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-his544 (accessed [today's date]).

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