Is CCND2 p.Val284Ala (c.851T>C) pathogenic?

CCND2 p.Val284Ala (c.851T>C) is classified Uncertain significance in CCND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). AlphaMissense: likely pathogenic (0.9736); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CCND2 p.Val284Ala (c.851T>C)?

CCND2 p.Val284Ala (c.851T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CCND2 p.Val284Ala (c.851T>C) in the general population?

CCND2 p.Val284Ala (c.851T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCND2 p.Val284Ala (c.851T>C)?

AlphaMissense predicts likely pathogenic (score 0.9736) — an in-silico prediction, not a clinical call.

CCND2 p.Val284Ala

c.851T>C · VCV3829084

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9736 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9736	likely pathogenic
REVEL	0.473	indeterminate
SaProt	LLR -7.01	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 108 bp · p 0.37 · regional, not allelic
Overall
CADD	26.1	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: CCND2
Protein: p.Val284Ala
Coding: c.851T>C
MANE Select: NM_001759
Type: single nucleotide variant
Location: chr12:4299990 (GRCh38)
Gene constraint: LOEUF 0.385 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.98 · 1 PDB
Residue 284: 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.Val284Glu Pathogenic/Likely pathogenic ★★ ⚠ same residue
CCND2 p.Val284Met Uncertain significance ★ ⚠ 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

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-val284ala (accessed [today's date]).

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