Is CDK19 p.Thr408= (c.1224C>T) pathogenic?

CDK19 p.Thr408= (c.1224C>T) is classified Likely benign in CDK19 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-01). Rare (popmax 0.403%, afr).

How common is CDK19 p.Thr408= (c.1224C>T) in the general population?

CDK19 p.Thr408= (c.1224C>T) is rare (popmax 0.403%, afr) (gnomAD).

CDK19 p.Thr408=

c.1224C>T · VCV3771299

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.403%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.6	GERP -5.4
Overall
CADD	0.297	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.403% African / African-American · 302/75,026 alleles

Filtering AF 0.365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.351%

Overall 0.0231% 372/1,613,168 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.403%	248
Admixed American	0.0167%	6,001
Remaining individualsnot grpmax-eligible	0.0144%	6,940
European (non-Finnish)	0.00407%	24,582
South Asian	0.0033%	30,339

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.Thr408=
Coding: c.1224C>T
MANE Select: NM_015076
Type: single nucleotide variant
Location: chr6:110621257 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 77.97
Residue 408: the 'disordered' region

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

Similar variants

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
CDK19 c.456+5G>A 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-thr408 (accessed [today's date]).

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