Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.2%, afr)
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 -0.42 | GERP -3.7 |
| Overall | ||
| CADD | 7.946 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.2%
African / African-American · 3,143/74,748 alleles
Filtering AF
4.08%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.03%
Overall
0.221%
3,563/1,612,218 alleles · low-frequency
exomes 1,841/1,460,004 · genomes 1,722/152,214 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.2% | 24 |
| Middle Eastern | 0.364% | 275 |
| Remaining individualsnot grpmax-eligible | 0.266% | 376 |
| Admixed American | 0.22% | 455 |
| South Asian | 0.0132% | 7,579 |
| European (non-Finnish) | 0.00755% | 13,252 |
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
- CCNA2
- Protein
- p.Pro74=
- Coding
- c.222C>A
- MANE Select
- NM_001237
- dbSNP
- rs3217760
- Type
- single nucleotide variant
- Location
- chr4:121822638 (GRCh38)
- Gene constraint
- LOEUF 0.183 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.80 · 115 PDB
- Residue 74
- the 'disordered' region
Similar variants
- EXOSC9 p.Ala438Val Uncertain significance ★★ ⚠ same type
- CCN1 c.277+50G>C Benign ★★ same type
- CCN1 c.64-124G>A Benign ★★ same type
- CCN1 c.-107C>A Benign ★★ same type
- CCN1 p.Ser316Cys Likely benign ★★ ⚠ same type
- CCN1 p.Tyr300= Benign ★★ same type
- CCNA2 c.*828C>G Benign ★★ same type
- CCNA2 p.Leu126= Benign ★★ 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/ccna2-p-pro74 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown