Is TNK2 p.Ser15= (c.45C>T) pathogenic?

TNK2 p.Ser15= (c.45C>T) is classified Benign in TNK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-03). Rare (popmax 0.572%, afr).

How common is TNK2 p.Ser15= (c.45C>T) in the general population?

TNK2 p.Ser15= (c.45C>T) is rare (popmax 0.572%, afr) (gnomAD).

TNK2 p.Ser15=

c.45C>T · rs150404773 · VCV1620097

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.572%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.006	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.5	GERP -4.5
Overall
CADD	5.284	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.572% African / African-American · 429/74,964 alleles

Filtering AF 0.528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.51%

Overall 0.0316% 510/1,612,844 alleles · rare exomes 257/1,460,612 · genomes 253/152,232 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.572%	175
Remaining individualsnot grpmax-eligible	0.0417%	2,400
Admixed American	0.0383%	2,609
Middle Eastern	0.0191%	5,224
South Asian	0.0165%	6,067
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598
Finnishnot grpmax-eligible	0.00156%	63,938
European (non-Finnish)	0.00119%	84,279

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.Ser15=
Coding: c.45C>T
MANE Select: NM_001382273
dbSNP: rs150404773
Type: single nucleotide variant
Location: chr3:195888544 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.41 · 18 PDB
Residue 15: the 'sam-like domain' region

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

Similar variants

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
TNK2 p.Ala676Thr 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-ser15 (accessed [today's date]).

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