Is TNK2 p.Pro795= (c.2385G>A) pathogenic?

TNK2 p.Pro795= (c.2385G>A) is classified Likely benign in TNK2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-26). Ultra-rare (popmax 0.0349%, afr); Associated with TNK2-related disorder.

What condition is associated with TNK2 p.Pro795= (c.2385G>A)?

TNK2 p.Pro795= (c.2385G>A) is associated with TNK2-related disorder (ClinVar).

How common is TNK2 p.Pro795= (c.2385G>A) in the general population?

TNK2 p.Pro795= (c.2385G>A) is ultra-rare (popmax 0.0349%, afr) (gnomAD).

TNK2 p.Pro795=

c.2385G>A · rs778397434 · VCV3044392

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0349%, afr)

Conditions

TNK2-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 -0.34	GERP -4.6, phastCons 0.012
Overall
CADD	1.614	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0349% African / African-American · 25/71,658 alleles

Filtering AF 0.0242% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0206%

Overall 0.00418% 64/1,529,582 alleles · ultra-rare exomes 55/1,377,764 · genomes 9/151,818 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0349%	2,866
Remaining individualsnot grpmax-eligible	0.022%	4,551
East Asian	0.00229%	43,672
European (non-Finnish)	0.00209%	47,868
South Asian	0.00126%	79,510

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.Pro795=
Coding: c.2385G>A
MANE Select: NM_001382273
dbSNP: rs778397434
Type: single nucleotide variant
Location: chr3:195867913 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.41 · 18 PDB
Residue 795: the 'disordered' region; the 'ebd domain' region

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

Disease context

TNK2-related disorder

Similar variants

TNK2 p.Pro795Leu Uncertain significance ★ ⚠ same residue
TNK2 p.Gly317Arg Uncertain significance ★★ ⚠ same condition
TNK2 p.Ser537Ile Uncertain significance ★★ ⚠ same condition
TNK2 c.-18-3798G>C Likely benign same condition
TNK2 c.-18-3821G>A Likely benign same condition
TNK2 c.-18-3877G>A Likely benign same condition
TNK2 p.Asp587= Likely benign same condition
TNK2 p.Gly512= Likely benign same condition

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-pro795 (accessed [today's date]).

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