Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.578%, 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 -9.7 | GERP -2.8 |
| Overall | ||
| CADD | 0.255 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.578%
African / African-American · 434/75,048 alleles
Filtering AF
0.533%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.516%
Overall
0.0349%
563/1,613,368 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.578% | 173 |
| Remaining individualsnot grpmax-eligible | 0.0752% | 1,329 |
| Admixed American | 0.0416% | 2,401 |
| South Asian | 0.0231% | 4,336 |
| European (non-Finnish) | 0.00297% | 33,714 |
| East Asian | 0.00223% | 44,874 |
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
- CDKN1A
- Protein
- p.Pro4=
- Coding
- c.12G>A
- MANE Select
- NM_000389
- dbSNP
- rs4986868
- Type
- single nucleotide variant
- Location
- chr6:36684113 (GRCh38)
- Gene constraint
- LOEUF 1.492 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.16 · 13 PDB
- Residue 4
- a UniProt-annotated variant site (in)
Similar variants
- CDKN1A p.Pro4Leu Benign ★ same residue
- CDKN1A p.Arg84Gln Likely benign ★★ same type
- CDKN1A p.Ser31= Likely benign ★★ same type
- CDKN1A p.Thr80= Likely benign ★★ same type
- CDKN1A p.Ala106Val Uncertain significance ★ ⚠ same type
- CDKN1A p.Arg20His Uncertain significance ★ ⚠ same type
- CDKN1A p.Arg32His Uncertain significance ★ ⚠ same type
- CDKN1A p.Arg46His Uncertain significance ★ ⚠ 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/cdkn1a-p-pro4 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown