Ankylosing spondylitis (AS) and Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome are both rare immune diseases lacking resolved genetic causes. In 2017, patients (310 AS, 30 PFAPA) and control groups (381) were investigated using a 32.2 Mb targeted liquid capture array and Illumina short-read sequencing. Analysis was performed using GATK best practices of the time and the hg19 reference. Technology advancements now provide the opportunity to reanalyse the data for both genetic and somatic variation. The latter has recently been reported to contribute to the pathogenesis of both inflammatory and immune-mediated disease, which can include AS and PFAPA. . We will use the fastqs generated in 2017, align these to hg38, and identify multiple forms of genetic variation in the germline and somatic genomes. Specifically, we will adapt the Clinical Genomics Uppsala’s exome pipeline to analyse the data (https://github.com/clinicalgenomics-uppsala/hastings_rd_wes). The validated pipeline will be used for alignment and variant detection (e.g., BWA-MEM, DeepVariant), mosaic variants (DeepSomatic followed by DeepMosaic and MosaicForecast), annotation (SNPEff with dbNSFP, dbSNP and other public databases, https://pcingola.github.io/SnpEff/snpeff/introduction/), compression (crumble.cram and spring), structural variant (e.g. exomedepth, cnvpytor, expansionhunter, tiddit, manta), and augmented to detect mobile elements (e.g. MELT and Scramble) and alternate splice detection (e.g., SpliceAI). All softwares are provided through a container, and the whole genome sequence version of the pipeline is available and currently in use on Bianca (Uppmax). Given the advancements in reference genome builds, functional annotation, and tools to analyse Illumina short-read data, we expect the current project to provide new insights into the genetics of rare immune conditions, such as AS and PFAPA.