Is EEF2K p.Arg664Trp (c.1990C>T) pathogenic?

EEF2K p.Arg664Trp (c.1990C>T) is classified Uncertain significance in EEF2K (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-09). AlphaMissense: likely benign (0.1241); Very rare (popmax 0.00666%, sas).

How common is EEF2K p.Arg664Trp (c.1990C>T) in the general population?

EEF2K p.Arg664Trp (c.1990C>T) is very rare (popmax 0.00666%, sas) (gnomAD).

What do computational predictors say about EEF2K p.Arg664Trp (c.1990C>T)?

AlphaMissense predicts likely benign (score 0.1241) — an in-silico prediction, not a clinical call.

EEF2K p.Arg664Trp

c.1990C>T · VCV3506781

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1241 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1241	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -11.76	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 58 kb · p 0.22 · regional, not allelic
Overall
CADD	25.0	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

Grpmax group 0.00666% South Asian · 6/90,038 alleles

Filtering AF 0.0052% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00475%

Overall 0.00541% 87/1,608,694 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00666%	15,006
European (non-Finnish)	0.00637%	15,702
Remaining individualsnot grpmax-eligible	0.00321%	31,130
African / African-American	0.00268%	37,316
East Asian	0.00225%	44,418
Admixed American	0.00169%	59,232

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.Arg664Trp
Coding: c.1990C>T
MANE Select: NM_013302
Type: single nucleotide variant
Location: chr16:22280298 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.36 · 10 PDB
Residue 664: an α-helix

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

Similar variants

EEF2K p.Arg664Gln Uncertain significance ★ ⚠ same residue
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

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-arg664trp (accessed [today's date]).

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