Is TNK2 p.Pro952= (c.2856G>A) pathogenic?

TNK2 p.Pro952= (c.2856G>A) is classified Likely benign in TNK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-27). Ultra-rare (popmax 0.0112%, nfe).

How common is TNK2 p.Pro952= (c.2856G>A) in the general population?

TNK2 p.Pro952= (c.2856G>A) is ultra-rare (popmax 0.0112%, nfe) (gnomAD).

TNK2 p.Pro952=

c.2856G>A · rs373754685 · VCV3002871

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, nfe)

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 1.6	GERP -1.6, phastCons 0.73
Overall
CADD	9.376	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0112% European (non-Finnish) · 132/1,176,592 alleles

Filtering AF 0.00963% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00907%

Overall 0.00953% 152/1,595,382 alleles · ultra-rare exomes 145/1,443,458 · genomes 7/151,924 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0226%	4,415
European (non-Finnish)grpmax	0.0112%	8,914
Admixed American	0.0034%	29,435
East Asian	0.00224%	44,652
South Asian	0.00222%	45,048
African / African-American	0.00134%	74,670

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro952=
Coding: c.2856G>A
MANE Select: NM_001382273
dbSNP: rs373754685
Type: single nucleotide variant
Location: chr3:195867442 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.41 · 18 PDB
Residue 952: the 'disordered' region

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

Similar variants

TNK2 p.Pro952Leu Likely benign ★ 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-pro952 (accessed [today's date]).

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