Is CDK13 p.Pro356Ala (c.1066C>G) pathogenic?

CDK13 p.Pro356Ala (c.1066C>G) is classified Benign/Likely benign in CDK13 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.0572); Rare (popmax 0.409%, nfe).

How common is CDK13 p.Pro356Ala (c.1066C>G) in the general population?

CDK13 p.Pro356Ala (c.1066C>G) is rare (popmax 0.409%, nfe) (gnomAD).

What do computational predictors say about CDK13 p.Pro356Ala (c.1066C>G)?

AlphaMissense predicts likely benign (score 0.0572) — an in-silico prediction, not a clinical call.

CDK13 p.Pro356Ala

c.1066C>G · rs17537669 · VCV446011

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0572 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.409%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0572	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -5.82	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 0.57	GERP -1.8, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 47 kb · p 8.4e-05 · regional, not allelic
Overall
CADD	12.31	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

Grpmax group 0.409% European (non-Finnish) · 4,593/1,121,720 alleles

Filtering AF 0.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.395%

Overall 0.337% 4,958/1,471,084 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.409%	244
Remaining individualsnot grpmax-eligible	0.264%	378
Admixed American	0.192%	521
Finnishnot grpmax-eligible	0.184%	543
African / African-American	0.0613%	1,632
Middle Eastern	0.0399%	2,508
South Asian	0.0111%	8,973
Ashkenazi Jewishnot grpmax-eligible	0.00445%	22,474
East Asian	0.00263%	37,974

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: CDK13
Protein: p.Pro356Ala
Coding: c.1066C>G
MANE Select: NM_003718
dbSNP: rs17537669
Type: single nucleotide variant
Location: chr7:39951707 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB
Residue 356: the 'disordered' region; a UniProt-annotated variant site (in)

Full CDK13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK13 p.Ala732Thr Likely pathogenic ★★ same type
CDK13 p.Arg1025Ter Pathogenic/Likely pathogenic ★★ same type
CDK13 p.Arg737Cys Pathogenic ★★ same type
CDK13 p.Arg751Gln Pathogenic/Likely pathogenic ★★ same type
CDK13 p.Arg860Gln Pathogenic/Likely pathogenic ★★ same type
CDK13 p.Arg880Cys Pathogenic/Likely pathogenic ★★ same type
CDK13 p.Asn842Asp Pathogenic/Likely pathogenic ★★ same type
CDK13 p.Asn842Ser Pathogenic/Likely pathogenic ★★ 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/cdk13-p-pro356ala (accessed [today's date]).

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