Is CDK2 p.Cys191Arg (c.571T>C) pathogenic?

CDK2 p.Cys191Arg (c.571T>C) is classified Uncertain significance in CDK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-02). AlphaMissense: likely pathogenic (0.9988); Absent from gnomAD v4.1.

How common is CDK2 p.Cys191Arg (c.571T>C) in the general population?

CDK2 p.Cys191Arg (c.571T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK2 p.Cys191Arg (c.571T>C)?

AlphaMissense predicts likely pathogenic (score 0.9988) — an in-silico prediction, not a clinical call.

CDK2 p.Cys191Arg

c.571T>C · VCV3999620

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9988 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9988	likely pathogenic
REVEL	0.584	indeterminate
SaProt	LLR -14.55	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 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.13	constrained · MANE · 626 bp · p 4.1e-08 · 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

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: CDK2
Protein: p.Cys191Arg
Coding: c.571T>C
MANE Select: NM_001798
Type: single nucleotide variant
Location: chr12:55969559 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.55 · 523 PDB
Residue 191: the protein kinase domain; an α-helix

Full CDK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK2 p.Arg199His Uncertain significance ★ ⚠ same type
CDK2 p.Arg200Gln Uncertain significance ★ ⚠ same type
CDK2 p.Arg200Trp Uncertain significance ★ ⚠ same type
CDK2 p.Arg214Gln Uncertain significance ★ ⚠ same type
CDK2 p.Asp288His Uncertain significance ★ ⚠ same type
CDK2 p.Glu57Ala Uncertain significance ★ ⚠ same type
CDK2 p.His268Leu Uncertain significance ★ ⚠ same type
CDK2 p.Ile10Leu 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/cdk2-p-cys191arg (accessed [today's date]).

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