Compositions and methods for improved SNP discrimination are provided. An exemplary composition comprises a programmable nuclease and a non-naturally occurring guide nucleic acid that hybridizes to a target nucleic acid, or segment thereof, comprising at least one single-nucleotide polymorphism (SNP). Methods may comprise a) contacting the sample to: i) a detector nucleic acid and ii) the composition; and b) assaying for a signal indicative of cleavage of the detector nucleic acid by the first programmable nuclease. In an exemplary embodiment, the target nucleic acid is a coronavirus target nucleic acid.