Is CDK13 p.Ser332Phe (c.995C>T) pathogenic?

CDK13 p.Ser332Phe (c.995C>T) is classified Likely benign in CDK13 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). AlphaMissense: likely benign (0.2667); Ultra-rare (popmax 0.0149%, sas).

How common is CDK13 p.Ser332Phe (c.995C>T) in the general population?

CDK13 p.Ser332Phe (c.995C>T) is ultra-rare (popmax 0.0149%, sas) (gnomAD).

What do computational predictors say about CDK13 p.Ser332Phe (c.995C>T)?

AlphaMissense predicts likely benign (score 0.2667) — an in-silico prediction, not a clinical call.

CDK13 p.Ser332Phe

c.995C>T · rs777406210 · VCV1986260

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2667 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0149%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2667	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -8.52	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 4.3	GERP 1.4, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 47 kb · p 8.4e-05 · regional, not allelic
Overall
CADD	24.6	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 0.0149% South Asian · 11/73,994 alleles

Filtering AF 0.00825% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0064%

Overall 0.00175% 26/1,481,544 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0149%	6,727
Admixed American	0.00247%	40,526
European (non-Finnish)	0.00125%	80,036

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.Ser332Phe
Coding: c.995C>T
MANE Select: NM_003718
dbSNP: rs777406210
Type: single nucleotide variant
Location: chr7:39951636 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB
Residue 332: the 'disordered' region

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-ser332phe (accessed [today's date]).

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