Is TNK2 p.Pro148= (c.444C>T) pathogenic?

TNK2 p.Pro148= (c.444C>T) is classified Likely benign in TNK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-15). Very rare (popmax 8.48e-05%, nfe).

How common is TNK2 p.Pro148= (c.444C>T) in the general population?

TNK2 p.Pro148= (c.444C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

TNK2 p.Pro148=

c.444C>T · rs545874058 · VCV1996890

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.087	GERP -3.8, phastCons 0.58
Overall
CADD	5.514	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,526 alleles

Overall 6.21e-05% 1/1,611,126 alleles · very rare exomes 1/1,458,850 · genomes 0/152,276 · joint denominator

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: TNK2
Protein: p.Pro148=
Coding: c.444C>T
MANE Select: NM_001382273
dbSNP: rs545874058
Type: single nucleotide variant
Location: chr3:195884824 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.41 · 18 PDB
Residue 148: the protein kinase domain; a β-strand

Full TNK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TNK2 p.Pro148His Uncertain significance ★ ⚠ same residue
TNK2 c.1162-3C>T Uncertain significance ★★ same type
TNK2 c.-18-6750C>T Uncertain significance ★★ same type
TNK2 c.-18-6791C>G Uncertain significance ★★ same type
TNK2 c.-18-6794C>A Uncertain significance ★★ same type
TNK2 p.Ala147Thr Uncertain significance ★★ ⚠ same type
TNK2 p.Ala601Thr Uncertain significance ★★ ⚠ same type
TNK2 p.Ala641Thr 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/tnk2-p-pro148 (accessed [today's date]).

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