Is TNK2 p.Pro522= (c.1566T>C) pathogenic?

TNK2 p.Pro522= (c.1566T>C) is classified Likely benign in TNK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-19). Ultra-rare (popmax 0.0244%, eas).

How common is TNK2 p.Pro522= (c.1566T>C) in the general population?

TNK2 p.Pro522= (c.1566T>C) is ultra-rare (popmax 0.0244%, eas) (gnomAD).

TNK2 p.Pro522=

c.1566T>C · rs182355191 · VCV2913113

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0244%, eas)

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 6.8	GERP 1.7, phastCons 1
Overall
CADD	11.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0244% East Asian · 10/40,920 alleles

Filtering AF 0.0132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.000709% 11/1,550,988 alleles · ultra-rare exomes 9/1,398,708 · genomes 2/152,280 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0244%	4,092
Remaining individualsnot grpmax-eligible	0.00166%	60,100

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.Pro522=
Coding: c.1566T>C
MANE Select: NM_001382273
dbSNP: rs182355191
Type: single nucleotide variant
Location: chr3:195869519 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.41 · 18 PDB
Residue 522: the 'disordered' region

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

Similar variants

TNK2 p.Pro522Ser 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-pro522 (accessed [today's date]).

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