We present Sprite, a new high-performance data analysis pipeline for detecting single nucleotide polymorphisms (SNPs) in the human genome. A SNP detection pipeline for next-generation sequencing data uses several software tools, including tools for read alignment, processing alignment output, and SNP identification. We target end-to-end scalability and I/O efficiency in Sprite by merging tools in this pipeline and eliminating redundancies. For a benchmark human whole-genome sequencing data set, Sprite takes less than 50 min on 16 nodes of the TACC Stampede supercomputer. A key component of our optimized pipeline is parsnip, a new parallel method and software tool for SNP detection. We find that the quality of results obtained by parsnip (sensitivity and precision using high-confidence variant calls as ground truth) is comparable to state-of-the-art SNP-calling software.