Is CCND2 p.Val284Met (c.850G>A) pathogenic?

CCND2 p.Val284Met (c.850G>A) is classified Uncertain significance in CCND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-13). AlphaMissense: likely pathogenic (0.8717); Very rare (popmax 0.0039%, nfe).

How common is CCND2 p.Val284Met (c.850G>A) in the general population?

CCND2 p.Val284Met (c.850G>A) is very rare (popmax 0.0039%, nfe) (gnomAD).

What do computational predictors say about CCND2 p.Val284Met (c.850G>A)?

AlphaMissense predicts likely pathogenic (score 0.8717) — an in-silico prediction, not a clinical call.

CCND2 p.Val284Met

c.850G>A · VCV4749422

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8717 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0039%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8717	likely pathogenic
REVEL	0.356	indeterminate
SaProt	LLR -7.78	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 108 bp · p 0.37 · regional, not allelic
Overall
CADD	27.6	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

Grpmax group 0.0039% European (non-Finnish) · 46/1,179,940 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00267%

Overall 0.00316% 51/1,613,886 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0039%	25,651
South Asian	0.0022%	45,538
Admixed American	0.00167%	59,980
Remaining individualsnot grpmax-eligible	0.0016%	62,482
African / African-American	0.00133%	74,916

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CCND2
Protein: p.Val284Met
Coding: c.850G>A
MANE Select: NM_001759
Type: single nucleotide variant
Location: chr12:4299989 (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

Similar variants

CCND2 p.Val284Glu Pathogenic/Likely pathogenic ★★ ⚠ same residue
CCND2 p.Val284Ala Uncertain significance ★ ⚠ same residue
CCND2 p.Gln277Ter Pathogenic/Likely pathogenic ★★ same type
CCND2 p.Pro281Ala Pathogenic ★★ same type
CCND2 p.Pro281Ser Pathogenic/Likely pathogenic ★★ same type
CCND2 p.Ser271Ter Likely pathogenic ★★ same type
CCND2 p.Thr280Ala Pathogenic ★★ same type
CCND2 p.Thr280Asn Pathogenic/Likely pathogenic ★★ 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/ccnd2-p-val284met (accessed [today's date]).

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