CCND2 p.Glu74=
c.222A>G · rs755257315 · VCV2715815
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0286%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.066 | GERP -3.7, phastCons 0.32 |
| Overall | ||
| CADD | 10.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0286%
South Asian · 26/90,976 alleles
Filtering AF
0.0199%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0171%
Overall
0.00291%
47/1,612,984 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0286% | 3,499 |
| Remaining individualsnot grpmax-eligible | 0.0192% | 5,206 |
| Admixed American | 0.0117% | 8,564 |
| East Asian | 0.00223% | 44,860 |
| African / African-American | 0.00134% | 74,786 |
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.Glu74=
- Coding
- c.222A>G
- MANE Select
- NM_001759
- dbSNP
- rs755257315
- Type
- single nucleotide variant
- Location
- chr12:4276031 (GRCh38)
- Gene constraint
- LOEUF 0.385 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 87.98 · 1 PDB
- Residue 74
- 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-glu74 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown