Is CCND2 p.Pro198Arg (c.593C>G) pathogenic?

CCND2 p.Pro198Arg (c.593C>G) is classified Uncertain significance in CCND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-20). AlphaMissense: likely pathogenic (0.8868); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CCND2 p.Pro198Arg (c.593C>G)?

CCND2 p.Pro198Arg (c.593C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CCND2 p.Pro198Arg (c.593C>G) in the general population?

CCND2 p.Pro198Arg (c.593C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCND2 p.Pro198Arg (c.593C>G)?

AlphaMissense predicts likely pathogenic (score 0.8868) — an in-silico prediction, not a clinical call.

CCND2 p.Pro198Arg

c.593C>G · rs1864058731 · VCV986248

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8868 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8868	likely pathogenic
REVEL	0.532	indeterminate
SaProt	LLR -11.40	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 6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 26 kb · p 7.7e-16 · regional, not allelic
Overall
CADD	27.9	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: CCND2
Protein: p.Pro198Arg
Coding: c.593C>G
MANE Select: NM_001759
dbSNP: rs1864058731
Type: single nucleotide variant
Location: chr12:4288863 (GRCh38)
Gene constraint: LOEUF 0.385 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.98 · 1 PDB

Full CCND2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CCND2 p.Pro198= Likely benign ★ same residue
CCND2 p.Pro281Ala Pathogenic ★★ same condition
CCND2 p.Arg178Cys Uncertain significance ★★ ⚠ same condition
CCND2 p.Ser222Leu Uncertain significance ★★ ⚠ same condition
CCND2 p.Gln215Ter Pathogenic ★ same condition
CCND2 p.Glu272Ter Pathogenic ★ same condition
CCND2 p.Ala120Ser Uncertain significance ★ ⚠ same condition
CCND2 p.Ala189Val Uncertain significance ★ ⚠ same condition

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/ccnd2-p-pro198arg (accessed [today's date]).

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