NM_003016.4:c.284_307del is an in-frame deletion of 24 nucleotides in SRSF2, resulting in loss of 8 amino acids (p.Pro95_Arg102del) at the boundary of the RRM and RS-rich domains.¹ The deletion meets PM4 (moderate) because it causes a protein length change through an in-frame deletion in a non-repetitive region, per ACMG/AMP 2015 guidelines.² BP3 is not met because the deleted region is non-repetitive and includes Pro95, a residue of established functional significance in SRSF2.³ PVS1 is not applicable: the variant is an in-frame deletion rather than a null variant. Per ClinGen SVI PVS1 recommendations, in-frame deletions are not eligible for PVS1 at any strength level.⁴ Population frequency data from gnomAD v2.1 and v4.1 are unavailable due to incomplete variant normalization in the pipeline. gnomAD-Canada reports AC=0, AN=0 (no data), precluding application of PM2, BA1, or BS1. Pro95 is a known somatic mutational hotspot in SRSF2 (ClinVar: P95H Pathogenic, P95L Pathogenic, P95R Likely pathogenic), but germline hotspot evidence for SRSF2 is not established, so PM1 is not met in this context.⁵ Multiple criteria (PS2, PS3, PS4, PM6, PP1, PP4, BS2, BS3, BS4, BP2, BP5, BP6) remain not_assessed due to absence of case-level, functional, segregation, or population data in the available evidence. Based on available evidence, the only applicable criterion is PM4 (moderate). The evidence is insufficient to reach a definitive classification; the variant defaults to Variant of Uncertain Significance (VUS) under generic ACMG/AMP 2015 combination rules.⁶