Abstract: Disclosed herein are methods, systems, and devices for detection of nucleotide variants. In some aspects, the methods, systems, and devices of the present disclosure can be used to detect germline variant or somatic variant in a biological sample, e.g., a sample from a tumor tissue. In other aspects, the methods, systems, and devices of the present disclosure can be used to detect somatic variant in cell-free nucleic acids from a biological sample, such as blood, plasma, serum, saliva, or urine. In some aspects, the methods, systems, and devices of the present disclosure make use of neural networks, such as convolutional neural networks for variant detection.