Is CDK13 p.Ser77Ala (c.229T>G) pathogenic?

CDK13 p.Ser77Ala (c.229T>G) is classified Benign/Likely benign in CDK13 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-01). AlphaMissense: likely benign (0.075); Ultra-rare (popmax 0.0268%, mid); Associated with Inborn genetic diseases.

What condition is associated with CDK13 p.Ser77Ala (c.229T>G)?

CDK13 p.Ser77Ala (c.229T>G) is associated with Inborn genetic diseases (ClinVar).

How common is CDK13 p.Ser77Ala (c.229T>G) in the general population?

CDK13 p.Ser77Ala (c.229T>G) is ultra-rare (popmax 0.0268%, mid) (gnomAD).

What do computational predictors say about CDK13 p.Ser77Ala (c.229T>G)?

AlphaMissense predicts likely benign (score 0.075) — an in-silico prediction, not a clinical call.

CDK13 p.Ser77Ala

c.229T>G · rs902762110 · VCV2919322

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.075 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0268%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.075	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -5.31	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 7.2	GERP 0.57, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 47 kb · p 8.4e-05 · regional, not allelic
Overall
CADD	23.9	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 0.0268% Middle Eastern · 1/3,734 alleles

Filtering AF 0.007% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0051%

Overall 0.00665% 91/1,367,938 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0268%	3,734
South Asian	0.0142%	7,023
Admixed American	0.0119%	8,401
Finnishnot grpmax-eligible	0.0101%	9,888
Remaining individualsnot grpmax-eligible	0.00957%	10,452
African / African-American	0.00765%	13,068
European (non-Finnish)	0.00607%	16,487

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.Ser77Ala
Coding: c.229T>G
MANE Select: NM_003718
dbSNP: rs902762110
Type: single nucleotide variant
Location: chr7:39950870 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB
Residue 77: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDK13 p.Ser77= Likely benign ★★ same residue
CDK13 p.Ala1301Val Uncertain significance ★★ ⚠ same condition
CDK13 p.Ala134Val Uncertain significance ★★ ⚠ same condition
CDK13 p.Ala182Val Uncertain significance ★★ ⚠ same condition
CDK13 p.Ala331Val Uncertain significance ★★ ⚠ same condition
CDK13 p.Ala504Val Uncertain significance ★★ ⚠ same condition
CDK13 p.Ala970Val Uncertain significance ★★ ⚠ same condition
CDK13 p.Arg1366Cys Uncertain significance ★★ ⚠ same condition

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-ser77ala (accessed [today's date]).

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