Genetic studies of chronic rhinosinusitis (CRS) have identified a total of 53 CRS-associated SNPs that were subsequently evaluated for their reproducibility in a recent study. The rs2873551 SNP in linkage disequilibrium with PARS2 showed the strongest association signal. The present study aims to comprehensively screen for rare variants in PARS2 and evaluate for accumulation of such variants in CRS-patients. Sanger sequencing and long-range PCR were used to screen for rare variants in the putative promoter region and coding sequence of 310 CRS-patients and a total of 21 variants were detected. The mutation spectrum was then compared with data from European populations of the 1000Genomes project (EUR) and the Exome Aggregation Consortium (ExAC). The CRS population showed a significant surplus of low-frequency variants compared with ExAC data. Haplotype analysis of the region showed a significant excess of rare haplotypes in the CRS population compared to the EUR population. Two missense mutations were also genotyped in the 310 CRS patients and 372 CRS-negative controls, but no associations with the disease were found. This is the first re-sequencing study in CRS research and also the first study to show an association of rare variants with the disease.