Is EEF2K p.Arg200Trp (c.598C>T) pathogenic?

EEF2K p.Arg200Trp (c.598C>T) is classified Uncertain significance in EEF2K (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely pathogenic (0.7923); Very rare (popmax 0.00668%, eas).

How common is EEF2K p.Arg200Trp (c.598C>T) in the general population?

EEF2K p.Arg200Trp (c.598C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about EEF2K p.Arg200Trp (c.598C>T)?

AlphaMissense predicts likely pathogenic (score 0.7923) — an in-silico prediction, not a clinical call.

EEF2K p.Arg200Trp

c.598C>T · VCV4831574

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7923 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7923	likely pathogenic
REVEL	0.375	indeterminate
SaProt	LLR -12.06	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.9, 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

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00668% East Asian · 3/44,886 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00161% 26/1,613,976 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,962
South Asian	0.00329%	30,361
Admixed American	0.00167%	59,986
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.00144%	69,412
African / African-American	0.00133%	74,942

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: EEF2K
Protein: p.Arg200Trp
Coding: c.598C>T
MANE Select: NM_013302
Type: single nucleotide variant
Location: chr16:22251302 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.36 · 10 PDB
Residue 200: the alpha-type protein kinase domain

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-arg200trp (accessed [today's date]).

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