Is EEF2 p.His705Tyr (c.2113C>T) pathogenic?

EEF2 p.His705Tyr (c.2113C>T) is classified Uncertain significance in EEF2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-05). AlphaMissense: likely benign (0.123); Very rare (popmax 0.00225%, eas).

How common is EEF2 p.His705Tyr (c.2113C>T) in the general population?

EEF2 p.His705Tyr (c.2113C>T) is very rare (popmax 0.00225%, eas) (gnomAD).

What do computational predictors say about EEF2 p.His705Tyr (c.2113C>T)?

AlphaMissense predicts likely benign (score 0.123) — an in-silico prediction, not a clinical call.

EEF2 p.His705Tyr

c.2113C>T · rs200627243 · VCV2026961

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.123 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00225%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.123	likely benign
REVEL	0.246	benign-leaning
SaProt	LLR -6.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 1,578 bp · p 7.1e-09 · regional, not allelic
Overall
CADD	19.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00225% East Asian · 1/44,460 alleles

Filtering AF 0.000364% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000263%

Overall 0.000776% 11/1,418,340 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00225%	44,460
African / African-American	0.00135%	74,280
European (non-Finnish)	0.000773%	129,396

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.His705Tyr
Coding: c.2113C>T
MANE Select: NM_001961
dbSNP: rs200627243
Type: single nucleotide variant
Location: chr19:3977565 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 26 PDB
Residue 705: a β-strand

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

Similar variants

EEF2 p.His705= Benign ★★ 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-his705tyr (accessed [today's date]).

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