Is CDK12 p.Arg272Ser (c.816G>T) pathogenic?

CDK12 p.Arg272Ser (c.816G>T) is classified Uncertain significance in CDK12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-20). AlphaMissense: likely pathogenic (0.8189); Absent from gnomAD v4.1.

How common is CDK12 p.Arg272Ser (c.816G>T) in the general population?

CDK12 p.Arg272Ser (c.816G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK12 p.Arg272Ser (c.816G>T)?

AlphaMissense predicts likely pathogenic (score 0.8189) — an in-silico prediction, not a clinical call.

CDK12 p.Arg272Ser

c.816G>T · VCV4651321

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8189 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8189	likely pathogenic
REVEL	0.24	benign-leaning
SaProt	LLR -6.43	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -0.27, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 8,924 bp · p 0.17 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDK12
Protein: p.Arg272Ser
Coding: c.816G>T
MANE Select: NM_016507
Type: single nucleotide variant
Location: chr17:39462887 (GRCh38)
Gene constraint: LOEUF 0.21 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.39 · 39 PDB
Residue 272: the 'disordered' region

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

Similar variants

CDK12 p.Arg272= Likely benign ★ same residue
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

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-arg272ser (accessed [today's date]).

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