Is CDK19 p.Ala395Val (c.1184C>T) pathogenic?

CDK19 p.Ala395Val (c.1184C>T) is classified Uncertain significance in CDK19 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.0748); Rare (popmax 0.248%, eas); Associated with microcephaly.

What condition is associated with CDK19 p.Ala395Val (c.1184C>T)?

CDK19 p.Ala395Val (c.1184C>T) is associated with microcephaly (ClinVar).

How common is CDK19 p.Ala395Val (c.1184C>T) in the general population?

CDK19 p.Ala395Val (c.1184C>T) is rare (popmax 0.248%, eas) (gnomAD).

What do computational predictors say about CDK19 p.Ala395Val (c.1184C>T)?

AlphaMissense predicts likely benign (score 0.0748) — an in-silico prediction, not a clinical call.

CDK19 p.Ala395Val

c.1184C>T · rs55914301 · VCV813559

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0748 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.248%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microcephaly

Computational evidence

Protein change
AlphaMissense	0.0748	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -7.21	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	GERP 0.95, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 8,332 bp · p 5.7e-06 · regional, not allelic
Overall
CADD	18.14	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 0.248% East Asian · 111/44,806 alleles

Filtering AF 0.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.196%

Overall 0.00938% 151/1,608,992 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.248%	404
Remaining individualsnot grpmax-eligible	0.037%	2,706
Admixed American	0.0151%	6,612
Finnishnot grpmax-eligible	0.00157%	63,838
European (non-Finnish)	0.000595%	168,157

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: CDK19
Protein: p.Ala395Val
Coding: c.1184C>T
MANE Select: NM_015076
dbSNP: rs55914301
Type: single nucleotide variant
Location: chr6:110621297 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 77.97
Residue 395: the 'disordered' region

Full CDK19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

microcephaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDK19 p.Ala395= Likely benign ★ same residue
CDK19 p.Thr196Ala Pathogenic/Likely pathogenic ★★ ⚠ same type
CDK19 p.Lys47Asn Uncertain significance ★★ ⚠ same type
CDK19 p.Pro495Thr Uncertain significance ★★ ⚠ same type
CDK19 p.Trp198Cys Uncertain significance ★★ ⚠ same type
CDK19 p.Arg200Gln Pathogenic ★ same type
CDK19 p.Arg200Trp Likely pathogenic ★ same type
CDK19 c.1111-4A>G Uncertain significance ★ 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/cdk19-p-ala395val (accessed [today's date]).

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