Is TNK2 p.Asp28= (c.84T>C) pathogenic?

TNK2 p.Asp28= (c.84T>C) is classified Benign in TNK2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Common (popmax 60.5%, afr) — too common for a highly-penetrant pathogenic allele.

TNK2 p.Asp28=

Q: How common is TNK2 p.Asp28= (c.84T>C) in the general population?

TNK2 p.Asp28= (c.84T>C) is common (popmax 60.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.84T>C · rs3747669 · VCV259882

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 60.5%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.512	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -4.5
Overall
CADD	0.886	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 60.5% African / African-American · 45,314/74,846 alleles

Filtering AF 60.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 59.9%

Overall 30.2% 487,814/1,612,956 alleles · common exomes 428,921/1,461,136 · genomes 58,893/151,820 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	60.5%	2
East Asian	42.9%	2
Middle Eastern	41.3%	2
Ashkenazi Jewishnot grpmax-eligible	41.2%	2
Admixed American	39%	3
Remaining individualsnot grpmax-eligible	33%	3
South Asian	30.2%	3
Finnishnot grpmax-eligible	29.2%	3
European (non-Finnish)	27%	4
Amishnot grpmax-eligible	25.3%	4

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.Asp28=
Coding: c.84T>C
MANE Select: NM_001382273
dbSNP: rs3747669
Type: single nucleotide variant
Location: chr3:195888505 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.41 · 18 PDB
Residue 28: 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-asp28 (accessed [today's date]).

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