Is CCND2 p.Pro281Ala (c.841C>G) pathogenic?

CCND2 p.Pro281Ala (c.841C>G) is classified Pathogenic in CCND2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-01). AlphaMissense: likely pathogenic (0.9755); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CCND2 p.Pro281Ala (c.841C>G)?

CCND2 p.Pro281Ala (c.841C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CCND2 p.Pro281Ala (c.841C>G) in the general population?

CCND2 p.Pro281Ala (c.841C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCND2 p.Pro281Ala (c.841C>G)?

AlphaMissense predicts likely pathogenic (score 0.9755) — an in-silico prediction, not a clinical call.

CCND2 p.Pro281Ala

c.841C>G · rs587777621 · VCV520663

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9755 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,038)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9755	likely pathogenic ✓ concordant with ClinVar
REVEL	0.749	pathogenic-leaning
SaProt	LLR -7.95	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 108 bp · p 0.37 · regional, not allelic
Overall
CADD	25.8	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

No allele count reported in gnomAD v4.1 (AN 1,614,038). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CCND2
Protein: p.Pro281Ala
Coding: c.841C>G
MANE Select: NM_001759
dbSNP: rs587777621
Type: single nucleotide variant
Location: chr12:4299980 (GRCh38)
Gene constraint: LOEUF 0.385 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.98 · 1 PDB
Residue 281: a UniProt-annotated variant site (in mpph3); the 'disordered' region

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.Pro281Ser Pathogenic/Likely pathogenic ★★ same residue
CCND2 p.Pro281Leu Pathogenic ★ same residue
CCND2 p.Pro281Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-pro281ala (accessed [today's date]).

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