Here, we show that ArCH can detect variants at low VAF (0.1%–1%) with high sensitivity and positive predictive value (PPV) using deep targeted sequencing datasets generated from acute myeloid leukemia (AML) tumor: normal dilutions (91.0% sensitivity; 83.0% PPV) and additional independently sequenced data with orthogonal validation (82.0% sensitivity; 95.0% PPV), while retaining 100% sensitivity and PPV for variants at higher VAF (>5%). The gene discussed is TSLIG1; the disease is acute myeloid leukemia.