Is EEF2K p.Trp486Cys (c.1458G>T) pathogenic?

EEF2K p.Trp486Cys (c.1458G>T) is classified Uncertain significance in EEF2K (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-13). AlphaMissense: likely pathogenic (0.8135); Absent from gnomAD v4.1.

How common is EEF2K p.Trp486Cys (c.1458G>T) in the general population?

EEF2K p.Trp486Cys (c.1458G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EEF2K p.Trp486Cys (c.1458G>T)?

AlphaMissense predicts likely pathogenic (score 0.8135) — an in-silico prediction, not a clinical call.

EEF2K p.Trp486Cys

c.1458G>T · rs2507170302 · VCV2483069

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8135 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8135	likely pathogenic
REVEL	0.495	indeterminate
SaProt	LLR -5.43	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.21	loss · gain 0.05 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 58 kb · p 0.22 · regional, not allelic
Overall
CADD	32.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EEF2K
Protein: p.Trp486Cys
Coding: c.1458G>T
MANE Select: NM_013302
dbSNP: rs2507170302
Type: single nucleotide variant
Location: chr16:22266407 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.36 · 10 PDB

Full EEF2K gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EEF2K p.Ala158Asp Uncertain significance ★ ⚠ same type
EEF2K p.Ala164Thr Uncertain significance ★ ⚠ same type
EEF2K p.Ala169Val Uncertain significance ★ ⚠ same type
EEF2K p.Ala306Val Uncertain significance ★ ⚠ same type
EEF2K p.Ala313Asp Uncertain significance ★ ⚠ same type
EEF2K p.Ala558Thr Uncertain significance ★ ⚠ same type
EEF2K p.Ala617Val Uncertain significance ★ ⚠ same type
EEF2K p.Ala644Thr 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/eef2k-p-trp486cys (accessed [today's date]).

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