Is TPRKB p.Leu151= (c.453C>T) pathogenic?

TPRKB p.Leu151= (c.453C>T) is classified Likely benign in TPRKB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-12-19). Very rare (popmax 0.00554%, nfe); Associated with TPRKB-related disorder.

What condition is associated with TPRKB p.Leu151= (c.453C>T)?

TPRKB p.Leu151= (c.453C>T) is associated with TPRKB-related disorder (ClinVar).

How common is TPRKB p.Leu151= (c.453C>T) in the general population?

TPRKB p.Leu151= (c.453C>T) is very rare (popmax 0.00554%, nfe) (gnomAD).

TPRKB p.Leu151=

c.453C>T · rs749784962 · VCV3048816

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00554%, nfe)

Conditions

TPRKB-related disorder

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 -11	GERP -3.4
Overall
CADD	0.181	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00554% European (non-Finnish) · 64/1,155,126 alleles

Filtering AF 0.00444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00404%

Overall 0.00421% 66/1,569,052 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00554%	18,049
Remaining individualsnot grpmax-eligible	0.00331%	30,175

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: TPRKB
Protein: p.Leu151=
Coding: c.453C>T
MANE Select: NM_033550 · reported on NM_016058
dbSNP: rs749784962
Type: single nucleotide variant
Location: chr2:73730018 (GRCh38)
Structure: AlphaFold pLDDT 91.58 · 6 PDB
Residue 151: the protein kinase domain; an α-helix

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

Disease context

TPRKB-related disorder

Similar variants

TPRKB p.Leu151Pro Uncertain significance ★ ⚠ same residue
TPRKB p.Asp50Tyr Uncertain significance ★ ⚠ same condition
TP53RK p.Leu186= Likely benign same condition
TPRKB p.Tyr109= Likely benign same condition
TP53RK p.Tyr112fs Conflicting classifications of pathogenicity ★ same condition
TPRKB c.-9_-7dup Likely benign same condition
TP53RK p.Arg243His Uncertain significance ★★ ⚠ same type
TP53RK p.Leu200Val 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/tprkb-p-leu151 (accessed [today's date]).

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