The nonsense variant NM_000448.3(RAG1):c.775del (p.Ser259AlafsTer5) occurs in exon 2 of 2 (the only coding exon of RAG1) and is not predicted to result in nonsense mediated decay but does truncate 75% of the protein, including the entirety of the core domain (amino acids 387-1011) which is critical to protein function (PMID: 26996199; PVS1). This variant is absent from gnomADv2.1.1 (PM2_Supporting). It has been reported homozygous in one patient with Omenn syndrome (PM3_supporting) with insufficient information to determine that the patient's phenotype is highly specific to recombinase activating gene 1 deficiency (PP4_NotMet). In summary, this variant meets the criteria to be classified as pathogenic for recombinase activating gene 1 deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP. Criteria applied: PVS1, PM3_Supporting, and PM2_Supporting. (VCEP specifications version 1).