CCND2 p.Cys46Ser
c.137G>C · VCV3371289
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.4458 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
0/2 damaging
REVEL, SaProt · AlphaMissense no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4458 | ambiguous |
|---|---|---|
| REVEL | 0.156 | moderately benign-leaning |
| SaProt | LLR -2.93 | tolerated |
| ⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>A here scores Δ0.49 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 9.6 | GERP 1, phastCons 1 |
| Regional constraint | o/e 0.55 | unconstrained · MANE · 26 kb · p 7.7e-16 · regional, not allelic |
| Overall | ||
| CADD | 24.9 | 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.Cys46Ser
- Coding
- c.137G>C
- MANE Select
- NM_001759
- Type
- single nucleotide variant
- Location
- chr12:4274177 (GRCh38)
- Gene constraint
- LOEUF 0.385 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 87.98 · 1 PDB
- Residue 46
- the cyclin n-terminal domain
Similar variants
- 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
- CCND2 p.Thr280Ile Pathogenic/Likely pathogenic ★★ ⚠ same type
- CCND2 p.Thr280Pro 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-cys46ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown