Is CDK10 p.Arg342His (c.1025G>A) pathogenic?

CDK10 p.Arg342His (c.1025G>A) is classified Uncertain significance in CDK10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-25). AlphaMissense: likely pathogenic (0.7077); Ultra-rare (popmax 0.0101%, amr); Associated with Inborn genetic diseases.

What condition is associated with CDK10 p.Arg342His (c.1025G>A)?

CDK10 p.Arg342His (c.1025G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CDK10 p.Arg342His (c.1025G>A) in the general population?

CDK10 p.Arg342His (c.1025G>A) is ultra-rare (popmax 0.0101%, amr) (gnomAD).

What do computational predictors say about CDK10 p.Arg342His (c.1025G>A)?

AlphaMissense predicts likely pathogenic (score 0.7077) — an in-silico prediction, not a clinical call.

CDK10 p.Arg342His

c.1025G>A · VCV3489138

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7077 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0101%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7077	likely pathogenic
REVEL	0.361	indeterminate
SaProt	LLR -7.57	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.2, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 8,978 bp · p 2.4e-06 · regional, not allelic
Overall
CADD	26.1	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 0.0101% Admixed American · 6/59,428 alleles

Filtering AF 0.00432% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00297%

Overall 0.00118% 19/1,605,042 alleles · ultra-rare exomes 13/1,452,832 · genomes 6/152,210 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0101%	9,905
African / African-American	0.00401%	24,907
South Asian	0.00223%	44,911
Finnishnot grpmax-eligible	0.00165%	60,600
European (non-Finnish)	0.000594%	168,211

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: CDK10
Protein: p.Arg342His
Coding: c.1025G>A
MANE Select: NM_052988
Type: single nucleotide variant
Location: chr16:89695634 (GRCh38)
Gene constraint: LOEUF 1.344 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.27
Residue 342: a UniProt-annotated variant site (in); the 'disordered' region

Full CDK10 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

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CDK10 p.Glu9Gln Uncertain significance ★★ ⚠ same condition
CDK10 p.Leu229Val Uncertain significance ★★ ⚠ same condition
CDK10 p.Leu269Val Uncertain significance ★★ same condition
CDK10 p.Met195Val Uncertain significance ★★ ⚠ same condition
CDK10 p.Val105Ile 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/cdk10-p-arg342his (accessed [today's date]).

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