NM_000222.2:c.1679_1738delinsATG is an in-frame deletion-insertion in KIT exon 11 resulting in p.Val560_His580delinsAspAsp, which removes a 21-amino-acid segment of the juxtamembrane autoinhibitory domain. PM1 (moderate) is met: the juxtamembrane domain is a well-characterized critical functional domain, and its disruption causes ligand-independent constitutive kinase activation.¹ PM2 (supporting) is met: the variant is absent from gnomAD v2.1 and v4.1 population databases.² PM4 (supporting) is met: a non-repeat in-frame deletion of 21 amino acids in a functionally critical domain.³ PVS1 is not applicable: this is an in-frame deletion-insertion, not a null variant eligible under ClinGen PVS1 decision tree criteria (PMC6185798).⁴ PS3 is not met: no variant-specific functional study directly testing p.Val560_His580delinsAspAsp was found in the provided literature. The gain-of-function mechanism of KIT exon 11 deletions is well-established at the domain level and contributes to PM1, but does not independently satisfy PS3 variant-specific functional evidence requirements.⁵ PS1, PS5, and PM5 are not applicable to this indel variant type. No benign criteria are met. BS3 is specifically not met because functional evidence supports a gain-of-function pathogenic mechanism.⁶ Total evidence: PM1 (moderate) + PM2 (supporting) + PM4 (supporting). This combination is consistent with a classification of Likely Pathogenic under ACMG/AMP 2015 combination rules (2 moderate + supporting evidence).⁷