Is CDK12 p.Glu1193Lys (c.3577G>A) pathogenic?

CDK12 p.Glu1193Lys (c.3577G>A) is classified Uncertain significance in CDK12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-21). AlphaMissense: likely benign (0.0925); Absent from gnomAD v4.1.

How common is CDK12 p.Glu1193Lys (c.3577G>A) in the general population?

CDK12 p.Glu1193Lys (c.3577G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK12 p.Glu1193Lys (c.3577G>A)?

AlphaMissense predicts likely benign (score 0.0925) — an in-silico prediction, not a clinical call.

CDK12 p.Glu1193Lys

c.3577G>A · VCV3830393

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0925 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0925	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -7.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 11 kb · p 0.0011 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Glu1193Lys
Coding: c.3577G>A
MANE Select: NM_016507
Type: single nucleotide variant
Location: chr17:39526133 (GRCh38)
Gene constraint: LOEUF 0.21 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.39 · 39 PDB

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

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-glu1193lys (accessed [today's date]).

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