CDK12 c.2963+252T>C
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 15.2%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +252 | deep intronic (+252 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.3 | GERP -2.4 |
| Non-coding constraint | Z -0.43 | 1 kb window · o/e 1.03 · regional · uncalibrated |
| Overall | ||
| CADD | 0.956 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
15.2%
African / African-American · 6,318/41,516 alleles
Filtering AF
14.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 14.8%
Overall
10.4%
15,851/152,196 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 15.2% | 7 |
| Remaining individualsnot grpmax-eligible | 11.2% | 9 |
| European (non-Finnish) | 9.71% | 10 |
| Middle Eastern | 8.9% | 11 |
| Amishnot grpmax-eligible | 8.13% | 12 |
| Finnishnot grpmax-eligible | 8.06% | 12 |
| Admixed American | 7.85% | 13 |
| Ashkenazi Jewishnot grpmax-eligible | 6.95% | 14 |
| East Asian | 3.03% | 33 |
| South Asian | 2.9% | 34 |
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
- CDK12
- Coding
- c.2963+252T>C
- MANE Select
- NM_016507
- dbSNP
- rs8068497
- Type
- single nucleotide variant
- Location
- chr17:39517808 (GRCh38)
- Gene constraint
- LOEUF 0.21 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 51.39 · 39 PDB
Similar variants
- CDK12 c.2108+56T>A Benign/Likely benign ★★ same type
- CDK12 c.2666+17A>C Benign ★★ same type
- CDK12 c.2769-74G>A Benign ★★ same type
- CDK12 c.2846+157G>T Benign ★★ same type
- CDK12 c.2963+111T>A Benign ★★ same type
- CDK12 c.2963+133G>A Benign ★★ same type
- CDK12 c.3308-116C>T Benign ★★ same type
- CDK12 c.3308-26A>G Likely 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/cdk12-c-2963-plus-252t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown