Is EEF2K p.Glu196Lys (c.586G>A) pathogenic?

EEF2K p.Glu196Lys (c.586G>A) is classified Uncertain significance in EEF2K (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-12). AlphaMissense: likely pathogenic (0.9001); Ultra-rare (popmax 0.0164%, mid).

How common is EEF2K p.Glu196Lys (c.586G>A) in the general population?

EEF2K p.Glu196Lys (c.586G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about EEF2K p.Glu196Lys (c.586G>A)?

AlphaMissense predicts likely pathogenic (score 0.9001) — an in-silico prediction, not a clinical call.

EEF2K p.Glu196Lys

c.586G>A · VCV4016344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9001 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9001	likely pathogenic
REVEL	0.315	indeterminate
SaProt	LLR -12.96	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.59 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 58 kb · p 0.22 · regional, not allelic
Overall
CADD	26.7	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 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000867% 14/1,614,030 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
African / African-American	0.00534%	18,735
Admixed American	0.005%	19,998
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.000424%	236,002

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.Glu196Lys
Coding: c.586G>A
MANE Select: NM_013302
Type: single nucleotide variant
Location: chr16:22251290 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.36 · 10 PDB
Residue 196: the alpha-type protein kinase domain; an α-helix

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-glu196lys (accessed [today's date]).

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