Disclosed are methods for detecting a minority genotype of a target nucleic acid. The disclosed method generally includes the steps of (a) deep sequencing at least a portion of the target nucleic acid; (b) using the deep sequencing results of (a) to detect the presence of variant nucleobases at one or more nucleotide reference positions within the target nucleic acid; (c) using the variant detection results generated in step (b) to perform a statistical analysis of whether the variants are significant; and (d) using the variant detection and variant significance results generated in steps (b) and (c) to perform a statistical analysis of whether a subset of sequences together exhibit a common set of significant variants.