CDKN2A c.-2A>T
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Conditions
1
hereditary neoplastic syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.204 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.46 | GERP -3.1 |
| Overall | ||
| CADD | 9.34 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,044 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000275%
4/1,454,376 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,044 |
| European (non-Finnish) | 0.000255% | 392,684 |
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
- Coding
- c.-2A>T
- MANE Select
- NM_000077 · reported on NM_058195
- dbSNP
- rs764949869
- Type
- single nucleotide variant
- Location
- chr9:21994333 (GRCh38)
- Gene constraint
- LOEUF 0.791 · pLI 0.62 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.02 · 5 PDB
Similar variants
- 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
- CDKN2A c.193+5G>A Pathogenic/Likely pathogenic ★★ same condition
- CDKN2A c.194-3653G>T Pathogenic ★★ same condition
- CDKN2A c.458-105A>G Pathogenic/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-c-minus-2a-t (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown