Is TNK2 p.Ser545= (c.1635C>T) pathogenic?

TNK2 p.Ser545= (c.1635C>T) is classified Benign in TNK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). Low-frequency (popmax 2.63%, afr).

How common is TNK2 p.Ser545= (c.1635C>T) in the general population?

TNK2 p.Ser545= (c.1635C>T) is low-frequency (popmax 2.63%, afr) (gnomAD).

TNK2 p.Ser545=

c.1635C>T · rs112740728 · VCV1601529

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.63%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.013	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2	GERP -4.1
Overall
CADD	4.861	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.63% African / African-American · 1,947/74,164 alleles

Filtering AF 2.53% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.49%

Overall 0.151% 2,399/1,593,238 alleles · low-frequency exomes 1,222/1,440,980 · genomes 1,177/152,258 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.63%	38
Admixed American	0.225%	444
Remaining individualsnot grpmax-eligible	0.211%	474
Middle Eastern	0.0997%	1,003
European (non-Finnish)	0.0141%	7,095
South Asian	0.0132%	7,567
East Asian	0.00677%	14,765

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.Ser545=
Coding: c.1635C>T
MANE Select: NM_001382273
dbSNP: rs112740728
Type: single nucleotide variant
Location: chr3:195868663 (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 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-ser545 (accessed [today's date]).

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