CDKN2A p.Val126=
c.378C>T · rs2131092754 · VCV1692141
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
Conditions
1
hereditary neoplastic syndrome
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 -1.1 | GERP -4 |
| Overall | ||
| CADD | 1.998 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,012 alleles
Overall
6.86e-05%
1/1,458,494 alleles · very rare
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
- CDKN2A
- Protein
- p.Val126=
- Coding
- c.378C>T
- MANE Select
- NM_000077
- dbSNP
- rs2131092754
- Type
- single nucleotide variant
- Location
- chr9:21970981 (GRCh38)
- Gene constraint
- LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.02 · 5 PDB
- Residue 126
- a UniProt-annotated variant site (in cmm2; impairs the function); an α-helix; the 'disordered' region
Similar variants
- CDKN2A p.Val126Asp Pathogenic ★★ same residue
- CDKN2A p.Val126Gly Uncertain significance ★★ ⚠ same residue
- CDKN2A p.Val126Leu Uncertain significance ★★ ⚠ same residue
- CDKN2A c.150+2T>G Likely pathogenic ★★ same condition
- CDKN2A c.151-1G>C Pathogenic ★★ same condition
- CDKN2A c.151-1G>T Pathogenic/Likely pathogenic ★★ same condition
- CDKN2A c.151-2A>G Pathogenic/Likely pathogenic ★★ same condition
- CDKN2A c.193+2T>C Likely pathogenic ★★ same condition
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/cdkn2a-p-val126 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown