Is CDK12 p.Arg1473Gln (c.4418G>A) pathogenic?

CDK12 p.Arg1473Gln (c.4418G>A) is classified Uncertain significance in CDK12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-22). AlphaMissense: likely benign (0.1082); Very rare (popmax 0.00965%, sas).

How common is CDK12 p.Arg1473Gln (c.4418G>A) in the general population?

CDK12 p.Arg1473Gln (c.4418G>A) is very rare (popmax 0.00965%, sas) (gnomAD).

What do computational predictors say about CDK12 p.Arg1473Gln (c.4418G>A)?

AlphaMissense predicts likely benign (score 0.1082) — an in-silico prediction, not a clinical call.

CDK12 p.Arg1473Gln

c.4418G>A · rs562860050 · VCV2598610

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1082 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00965%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1082	likely benign
REVEL	0.542	indeterminate
SaProt	LLR -7.84	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 2.2, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 247 bp · p 0.2 · regional, not allelic
Overall
CADD	24.5	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

Grpmax group 0.00965% South Asian · 7/72,554 alleles

Filtering AF 0.0045% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00334%

Overall 0.00424% 64/1,510,454 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00965%	10,365
European (non-Finnish)	0.00477%	20,974
African / African-American	0.00279%	35,810
East Asian	0.0023%	43,536

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.Arg1473Gln
Coding: c.4418G>A
MANE Select: NM_016507
dbSNP: rs562860050
Type: single nucleotide variant
Location: chr17:39531261 (GRCh38)
Gene constraint: LOEUF 0.21 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.39 · 39 PDB
Residue 1473: the 'disordered' region

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

Similar variants

CDK12 p.Arg1473Gly Uncertain significance ★ same residue
CDK12 p.Arg1473Pro Uncertain significance ★ ⚠ same residue
CDK12 p.Arg1473Trp Uncertain significance ★ ⚠ same residue
CDK12 p.Arg1473= 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

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-arg1473gln (accessed [today's date]).

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