The ASXL1 c.2822del (p.(Pro941LeufsTer4)) variant has been observed in somatic cancers and is absent from ClinVar.¹ This variant is absent from gnomAD v2.1 and gnomAD v4.1, corresponding to an observed population frequency of 0, which is below the 0.1% PM2 threshold and supports rarity in the general population.² Published studies and OncoKB support damaging loss-of-function biology for ASXL1 truncating variants, but available data do not provide a validated germline functional assay for this specific variant.³ This single-base deletion causes a frameshift predicted to truncate the protein after four altered amino acids, removing 598 of 1542 residues (38.8%), and SpliceAI predicts no significant additional splice effect with a maximum delta score of 0.02.⁴