Is TNK2 p.Pro595= (c.1785G>A) pathogenic?

TNK2 p.Pro595= (c.1785G>A) is classified Likely benign in TNK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-20). Ultra-rare (popmax 0.0281%, eas).

How common is TNK2 p.Pro595= (c.1785G>A) in the general population?

TNK2 p.Pro595= (c.1785G>A) is ultra-rare (popmax 0.0281%, eas) (gnomAD).

TNK2 p.Pro595=

c.1785G>A · rs200923684 · VCV2137543

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0281%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.03	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -4.4
Overall
CADD	0.061	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0281% East Asian · 12/42,682 alleles

Filtering AF 0.0161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0127%

Overall 0.0036% 56/1,556,486 alleles · ultra-rare exomes 48/1,404,250 · genomes 8/152,236 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0281%	3,557
Admixed American	0.0118%	8,454
Remaining individualsnot grpmax-eligible	0.00496%	20,143
European (non-Finnish)	0.00276%	36,256
South Asian	0.0023%	43,475
African / African-American	0.00136%	73,364

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.Pro595=
Coding: c.1785G>A
MANE Select: NM_001382273
dbSNP: rs200923684
Type: single nucleotide variant
Location: chr3:195868513 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.41 · 18 PDB

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

Similar variants

TNK2 p.Pro595Gln Uncertain significance ★ ⚠ same residue
TNK2 p.Pro595Leu 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

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-pro595 (accessed [today's date]).

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