Is CDK1 p.Arg215Lys (c.644G>A) pathogenic?

CDK1 p.Arg215Lys (c.644G>A) is classified Uncertain significance in CDK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: ambiguous (0.4115); Absent from gnomAD v4.1.

How common is CDK1 p.Arg215Lys (c.644G>A) in the general population?

CDK1 p.Arg215Lys (c.644G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK1 p.Arg215Lys (c.644G>A)?

AlphaMissense predicts ambiguous (score 0.4115) — an in-silico prediction, not a clinical call.

CDK1 p.Arg215Lys

c.644G>A · VCV4224154

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4115 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4115	ambiguous
REVEL	0.325	indeterminate
SaProt	LLR -6.33	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 8,219 bp · p 7.3e-18 · regional, not allelic
Overall
CADD	23.3	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: CDK1
Protein: p.Arg215Lys
Coding: c.644G>A
MANE Select: NM_001786
Type: single nucleotide variant
Location: chr10:60792044 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 89.52 · 14 PDB
Residue 215: the protein kinase domain; an α-helix

Full CDK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK1 p.Gln28Arg Uncertain significance ★ ⚠ same type
CDK1 p.His23Asn Uncertain significance ★ ⚠ same type
CDK1 p.Ile157Leu Uncertain significance ★ ⚠ same type
CDK1 p.Ile157Val Uncertain significance ★ ⚠ same type
CDK1 p.Ile190Val Uncertain significance ★ ⚠ same type
CDK1 p.Leu70Val Uncertain significance ★ ⚠ same type
CDK1 p.Lys279Arg Uncertain significance ★ ⚠ same type
CDK1 p.Ser121Thr 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/cdk1-p-arg215lys (accessed [today's date]).

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