Is EEF2 p.Leu729Phe (c.2185C>T) pathogenic?

EEF2 p.Leu729Phe (c.2185C>T) is classified Uncertain significance in EEF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). AlphaMissense: ambiguous (0.3625); Very rare (popmax 0.00134%, afr).

How common is EEF2 p.Leu729Phe (c.2185C>T) in the general population?

EEF2 p.Leu729Phe (c.2185C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about EEF2 p.Leu729Phe (c.2185C>T)?

AlphaMissense predicts ambiguous (score 0.3625) — an in-silico prediction, not a clinical call.

EEF2 p.Leu729Phe

c.2185C>T · rs1163697035 · VCV2649020

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3625 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Computational evidence

Protein change
AlphaMissense	0.3625	ambiguous
REVEL	0.299	indeterminate
SaProt	LLR -8.08	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 1,578 bp · p 7.1e-09 · regional, not allelic
Overall
CADD	21.7	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

Grpmax group 0.00134% African / African-American · 1/74,708 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000314% 5/1,589,832 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,708
European (non-Finnish)	0.000341%	293,282

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.Leu729Phe
Coding: c.2185C>T
MANE Select: NM_001961
dbSNP: rs1163697035
Type: single nucleotide variant
Location: chr19:3977493 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 26 PDB
Residue 729: an α-helix

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

Similar variants

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
EEF2 p.Arg726Trp 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-leu729phe (accessed [today's date]).

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