Is EEF2 p.Phe825Leu (c.2475C>A) pathogenic?

EEF2 p.Phe825Leu (c.2475C>A) is classified Uncertain significance in EEF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-28). AlphaMissense: ambiguous (0.4767); Absent from gnomAD v4.1.

How common is EEF2 p.Phe825Leu (c.2475C>A) in the general population?

EEF2 p.Phe825Leu (c.2475C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EEF2 p.Phe825Leu (c.2475C>A)?

AlphaMissense predicts ambiguous (score 0.4767) — an in-silico prediction, not a clinical call.

EEF2 p.Phe825Leu

c.2475C>A · rs781600560 · VCV2446641

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4767 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,609,624)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4767	ambiguous
REVEL	0.267	benign-leaning
SaProt	LLR -0.11	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.1	GERP -4.4
Regional constraint	o/e 0.71	unconstrained · MANE · 1,578 bp · p 7.1e-09 · regional, not allelic
Overall
CADD	0.227	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 1,609,624). 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.Phe825Leu
Coding: c.2475C>A
MANE Select: NM_001961
dbSNP: rs781600560
Type: single nucleotide variant
Location: chr19:3976656 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 26 PDB
Residue 825: a β-strand

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-phe825leu (accessed [today's date]).

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