CDKN2B p.Leu115=
c.343C>T · rs372284765 · VCV2576498
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0336%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 8.3 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 13.19 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0336%
Middle Eastern · 2/5,946 alleles
Filtering AF
0.00622%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00467%
Overall
0.00131%
21/1,606,034 alleles · ultra-rare
exomes 21/1,453,636 · genomes 0/152,398 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0336% | 2,973 |
| African / African-American | 0.012% | 8,341 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,789 |
| European (non-Finnish) | 0.000593% | 168,523 |
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
- CDKN2B
- Protein
- p.Leu115=
- Coding
- c.343C>T
- MANE Select
- NM_004936
- dbSNP
- rs372284765
- Type
- single nucleotide variant
- Location
- chr9:22006061 (GRCh38)
- Gene constraint
- LOEUF 1.836 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.12
Similar variants
- CDKN2B c.157-102G>A Benign ★★ same type
- CDKN2B c.157-27C>A Benign ★★ same type
- CDKN2B p.Ala120= Benign ★★ same type
- CDKN2B p.Ala129Gly Uncertain significance ★ ⚠ same type
- CDKN2B p.Ala129Val Uncertain significance ★ ⚠ same type
- CDKN2B p.Ala23Val Uncertain significance ★ ⚠ same type
- CDKN2B p.Ala50Val Uncertain significance ★ ⚠ same type
- CDKN2B p.Ala59Val 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/cdkn2b-p-leu115 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown