Is TNK2 p.Pro103= (c.309C>T) pathogenic?

TNK2 p.Pro103= (c.309C>T) is classified Likely benign in TNK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-08). Very rare (popmax 0.00834%, amr).

How common is TNK2 p.Pro103= (c.309C>T) in the general population?

TNK2 p.Pro103= (c.309C>T) is very rare (popmax 0.00834%, amr) (gnomAD).

TNK2 p.Pro103=

c.309C>T · VCV3665953

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

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 0.031	GERP -4.1, phastCons 0.5
Overall
CADD	8.638	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00834% Admixed American · 5/59,978 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00304% 49/1,613,716 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,996
East Asian	0.00446%	22,428
European (non-Finnish)	0.00331%	30,253
Remaining individualsnot grpmax-eligible	0.0032%	31,237
African / African-American	0.00133%	74,914

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.Pro103=
Coding: c.309C>T
MANE Select: NM_001382273
Type: single nucleotide variant
Location: chr3:195884959 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.41 · 18 PDB
Residue 103: the 'sam-like domain' region; the 'disordered' 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-pro103 (accessed [today's date]).

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