Our package performs competitively in its shared features of annotating and querying VCF files. We compared the efficiency of VariantAnnotation and SEQMINER for annotating large‐scale datasets and extracting genetic regions of interest (Tables 2 and 3): first, using 1,092 samples from the 1000 Genomes Project, we compared time and memory efficiency for annotating whole chromosome variants. In all scenarios examined, SEQMINER was >20× faster and required ∼100‐fold less memory than VariantAnnotation. We then benchmarked the extraction of nonsynonymous variants from 100 randomly selected genes. VariantAnnotation used 23.0 min and 1,095 MB memory, while SEQMINER used 1.3 min and 37 MB memory. In all scenarios considered, SEQMINER exhibited advantages in time and memory efficiency.