Is TNK2 p.Pro712= (c.2136G>A) pathogenic?

TNK2 p.Pro712= (c.2136G>A) is classified Likely benign in TNK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-01). Ultra-rare (popmax 0.0493%, mid).

How common is TNK2 p.Pro712= (c.2136G>A) in the general population?

TNK2 p.Pro712= (c.2136G>A) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

TNK2 p.Pro712=

c.2136G>A · rs768623108 · VCV3025409

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

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 -15	GERP -4.7
Overall
CADD	0.103	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0493% Middle Eastern · 3/6,080 alleles

Filtering AF 0.0142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0113%

Overall 0.00764% 123/1,609,672 alleles · ultra-rare exomes 112/1,457,608 · genomes 11/152,064 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,027
Admixed American	0.0235%	4,259
Remaining individualsnot grpmax-eligible	0.00802%	12,464
European (non-Finnish)	0.00797%	12,541
African / African-American	0.00668%	14,962
East Asian	0.00223%	44,776
South Asian	0.0011%	90,732

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.Pro712=
Coding: c.2136G>A
MANE Select: NM_001382273
dbSNP: rs768623108
Type: single nucleotide variant
Location: chr3:195868162 (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.Pro712Leu 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-pro712 (accessed [today's date]).

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