CDK12 p.Ala594=
c.1782T>C · VCV3489310
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0178%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>A here scores Δ0.20 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4.2 | GERP 0.83, phastCons 1 |
| Overall | ||
| CADD | 11.27 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0178%
East Asian · 8/44,884 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00811%
Overall
0.00285%
46/1,614,206 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0178% | 5,611 |
| African / African-American | 0.0173% | 5,773 |
| South Asian | 0.0154% | 6,506 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,930 |
| European (non-Finnish) | 0.000339% | 295,010 |
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
- Protein
- p.Ala594=
- Coding
- c.1782T>C
- MANE Select
- NM_016507
- Type
- single nucleotide variant
- Location
- chr17:39471614 (GRCh38)
- Gene constraint
- LOEUF 0.21 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 51.39 · 39 PDB
- Residue 594
- the 'disordered' region
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-p-ala594 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown