# NM_001039803.3(CDK20):c.615G>A (p.Pro205=)

https://sugi.bio/variant/cdk20-p-pro205

## Summary

**CDK20 p.Pro205= (c.615G>A)** is classified **Benign** in CDK20 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2018-06-13). Low-frequency (popmax 4.18%, afr).

**At a glance:** Benign · review: Multiple submitters · rsID rs28364959 · 4 submitters · low-frequency (popmax 4.18%, afr)

## For patients & families {#patients}

This is a change in the CDK20 gene that is classified as benign — not considered disease-causing, submitted by 4 submitters.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [CDK20](https://sugi.bio/atlas/gene/CDK20/) |
| Protein change (HGVS p.) | p.Pro205= |
| Coding change (HGVS c.) | c.615G>A |
| MANE Select transcript | [NM_001039803](https://www.ncbi.nlm.nih.gov/nuccore/NM_001039803) |
| dbSNP | [rs28364959](https://www.ncbi.nlm.nih.gov/snp/rs28364959/) |
| Variant type | single nucleotide variant |
| Location | chr9:87969868-87969868 (GRCh38) |
| ClinVar | [VCV768313](https://www.ncbi.nlm.nih.gov/clinvar/variation/768313/) |

**All HGVS expressions:** `NC_000009.11:g.90584783C>T`, `NC_000009.12:g.87969868C>T`, `NM_001039803.3:c.615G>A`, `NM_001170639.2:c.552G>A`, `NM_001170640.2:c.501-519G>A`, `NM_012119.5:c.552G>A`, `NM_178432.4:c.591G>A`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation and, for splice-region changes, SpliceAI (below), not from a missing predictor score.
- SpliceAI predicts **acceptor gain** (Δ 0.33) — a splice-altering prediction the current classification does not reflect
- Conservation: phyloP -5.252 — fast-evolving / accelerated position
- CADD: **PHRED 15.14**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI deltas (raw): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.33**, donor gain **0.09**. Largest is acceptor gain.
- SpliceAI deltas (masked): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.33**, donor gain **0.09**.
- Population frequency (gnomAD v4.1): grpmax **4.18%** (afr) · FAF95 4.06% · FAF99 4.01% · 3,131/74,816 in the highest group · 3,780/1,607,388 alleles overall — low-frequency (popmax 4.18%, afr).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| African / African-American (grpmax) | 4.18% | 24 |
| Middle Eastern | 0.432% | 232 |
| Remaining individuals (not grpmax-eligible) | 0.404% | 248 |
| Admixed American | 0.385% | 260 |
| South Asian | 0.0211% | 4,739 |
| European (non-Finnish) | 0.0102% | 9,804 |
| East Asian | 0.00447% | 22,371 |
| Ashkenazi Jewish (not grpmax-eligible) | 0.00344% | 29,054 |
| Finnish (not grpmax-eligible) | 0.00313% | 31,929 |

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**CDK20** population constraint: LOEUF 1.342, pLI 1.4576e-14, missense-Z -1.0434. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}

Residue **205** lies in the protein kinase domain.

AlphaFold model confidence (whole protein): pLDDT 86.08, 64% of residues very-high.

## Clinical significance {#significance}

**Benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2018-06-13.

**Submitter consensus:** unanimous (3/3 Benign).

**Submission history:** 8 submissions (2018–2019); classifications have differed over time.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| PreventionGenetics, part of Exact Sciences | Benign | no assertion criteria provided | clinical testing | 2019-11-11 |
| Labcorp Genetics (formerly Invitae), Labcorp | Benign | criteria provided, single submitter | clinical testing | 2018-06-13 |
| Breakthrough Genomics, Breakthrough Genomics | Benign | criteria provided, single submitter | not provided |  |
| Dr. Peter K. Rogan Lab, Western University |  | no classification provided | in vitro |  |

**Reported phenotype names (ClinVar):** not provided, CDK20-related disorder, Lung cancer, Cervical cancer, Clear cell carcinoma of kidney, Ovarian serous cystadenocarcinoma, Gastric cancer, none provided, CDK20-related condition.

## Similar variants {#similar}

Related CDK20 variant pages (same residue, condition, or type): [CDK20 p.Phe204Leu](/variant/cdk20-p-phe204leu), [CDK20 c.189+23G>C](/variant/cdk20-c-189-plus-23g-c), [CDK20 c.378+19C>T](/variant/cdk20-c-378-plus-19c-t), [CDK20 c.564-44C>T](/variant/cdk20-c-564-minus-44c-t), [CDK20 c.688-214G>A](/variant/cdk20-c-688-minus-214g-a), [CDK20 c.76-20G>T](/variant/cdk20-c-76-minus-20g-t), [CDK20 c.76-66T>C](/variant/cdk20-c-76-minus-66t-c), [CDK20 c.*153C>T](/variant/cdk20-c-star-153c-t).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-15); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 768313). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*