Is PLK2 p.Glu668Lys (c.2002G>A) pathogenic?

PLK2 p.Glu668Lys (c.2002G>A) is classified Uncertain significance in PLK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). AlphaMissense: likely benign (0.2714); Absent from gnomAD v4.1.

How common is PLK2 p.Glu668Lys (c.2002G>A) in the general population?

PLK2 p.Glu668Lys (c.2002G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLK2 p.Glu668Lys (c.2002G>A)?

AlphaMissense predicts likely benign (score 0.2714) — an in-silico prediction, not a clinical call.

PLK2 p.Glu668Lys

c.2002G>A · rs1743549633 · VCV3215319

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2714 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2714	likely benign
REVEL	0.206	benign-leaning
SaProt	LLR -7.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 1,010 bp · p 2.2e-06 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

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: PLK2
Protein: p.Glu668Lys
Coding: c.2002G>A
MANE Select: NM_006622
dbSNP: rs1743549633
Type: single nucleotide variant
Location: chr5:58454639 (GRCh38)
Gene constraint: LOEUF 0.471 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.64 · 7 PDB
Residue 668: the polo box 2 domain; an α-helix

Full PLK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PLK2 p.Ile595Thr Likely benign ★★ same type
PLK2 p.Ala12Thr Uncertain significance ★ ⚠ same type
PLK2 p.Ala12Val Uncertain significance ★ ⚠ same type
PLK2 p.Ala434Thr Uncertain significance ★ ⚠ same type
PLK2 p.Ala54Val Uncertain significance ★ ⚠ same type
PLK2 p.Ala55Val Uncertain significance ★ ⚠ same type
PLK2 p.Arg183Ter Uncertain significance ★ same type
PLK2 p.Arg596Gln 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/plk2-p-glu668lys (accessed [today's date]).

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