Is CDK12 p.Ser238= (c.714G>A) pathogenic?

CDK12 p.Ser238= (c.714G>A) is classified Benign in CDK12 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2022-04-19). Common (popmax 18.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with CDK12 p.Ser238= (c.714G>A)?

CDK12 p.Ser238= (c.714G>A) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CDK12 p.Ser238=

Q: How common is CDK12 p.Ser238= (c.714G>A) in the general population?

CDK12 p.Ser238= (c.714G>A) is common (popmax 18.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.714G>A · rs35896550 · VCV1250047

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 18.1%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

hereditary breast ovarian cancer 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 -5.2	GERP -3.5
Overall
CADD	0.583	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.1% African / African-American · 13,604/74,970 alleles

Filtering AF 17.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.8%

Overall 0.971% 15,665/1,614,046 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	18.1%	6
Admixed American	1.35%	74
Remaining individualsnot grpmax-eligible	1.3%	77
Middle Eastern	0.379%	264
South Asian	0.0769%	1,301
Finnishnot grpmax-eligible	0.0547%	1,829
European (non-Finnish)	0.026%	3,844
East Asian	0.0111%	8,974

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.Ser238=
Coding: c.714G>A
MANE Select: NM_016507
dbSNP: rs35896550
Type: single nucleotide variant
Location: chr17:39462785 (GRCh38)
Gene constraint: LOEUF 0.21 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.39 · 39 PDB
Residue 238: the 'disordered' region

Full CDK12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary breast ovarian cancer syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

CDK12 p.Ser238Leu Uncertain significance ★ ⚠ same residue
CDK12 p.Ser238Thr Uncertain significance ★ ⚠ same residue
CDK12 c.2108+56T>A Benign/Likely benign ★★ same condition
CDK12 c.2666+17A>C Benign ★★ same condition
CDK12 c.2769-74G>A Benign ★★ same condition
CDK12 c.3308-26A>G Likely benign ★★ same condition
CDK12 p.Arg1008= Likely benign ★★ same condition
CDK12 p.Arg322= Likely benign ★★ 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/cdk12-p-ser238 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown