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Conventional assays often require labels or provide ensemble\u2010averaged readouts, limiting their ability to resolve subtle variant differences. Here, a YaxAB nanopore workflow is presented for label\u2010free single\u2010molecule current fingerprinting of wild\u2010type Bcl\u2010xL and the cancer\u2010associated single\u2010residue variants N136K and R165W. Individual Bcl\u2010xL proteins were electro\u2010osmotically trapped within the funnel\u2010shaped YaxAB lumen, where they generated characteristic ionic\u2010current events. These events formed reproducible, analyte\u2010specific event populations in normalized current blockade and current noise space, resolving wild\u2010type Bcl\u2010xL, N136K, and R165W as distinct single\u2010molecule current fingerprints. Wild\u2010type Bcl\u2010xL and N136K remained distinct despite a mass difference of only 14\u00a0Da, and the fingerprint separation was consistent with combined differences in excluded volume, net charge, and dipole moment. Concentration\u2010dependent capture\u2010rate analysis further supported sub\u2010nanomolar to low\u2010nanomolar detection corresponding to protein amounts in the sub\u2010picomole to low\u2010picomole range, while capture\u2010rate normalization brought the estimated concentrations closer to the nominal concentrations. These results present YaxAB nanopore sensing as a label\u2010free single\u2010molecule workflow for the current fingerprinting of cancer\u2010associated single\u2010residue Bcl\u2010xL variants, with low\u2010concentration detection as a supporting analytical capability.<\/jats:p>","DOI":"10.1002\/smtd.71126","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T08:26:11Z","timestamp":1791966371000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Label\u2010Free YaxAB Nanopore Fingerprinting of Cancer\u2010Associated Single\u2010Residue Bcl\u2010xL Variants"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3200-0932","authenticated-orcid":false,"given":"Minji","family":"Chung","sequence":"first","affiliation":[{"name":"Orphan Disease Therapeutic Target Research Center, Division of A.I. and Biomedical Research Korea Research Institute of Bioscience and 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