NM_000077.4:c.52_83del is a 32 bp frameshift deletion in exon 1 of CDKN2A predicted to produce a truncated protein (p.Thr18AlafsTer15) that removes all four ankyrin-repeat domains and the CDK4/6 binding region of p16INK4A, meeting PVS1 at very strong strength under the ClinGen SVI PVS1 framework (PMC6185798).¹ The variant is absent from gnomAD v2.1, v4.1, and Canada population databases, satisfying PM2 at moderate strength.² The variant completely removes the well-characterized ankyrin-repeat and CDK4/6 binding domains of p16INK4A, meeting PM1 at moderate strength. Published functional studies demonstrate that N-terminal deletions and premature termination mutants of p16INK4A abolish CDK4/6 binding and kinase inhibitory activity.³ No functional study directly tested NM_000077.4:c.52_83del; PS3 is not met. Existing truncation data from PMID:8603820 (deletion constructs) and PMID:8668202 (premature termination mutants) provide domain-level evidence applied under PM1 rather than variant-specific PS3.⁴ ClinVar classifies this variant as 'Likely oncogenic' (somatic, 1-star single submitter) under variation ID 4539651. This somatic classification and review status do not satisfy PP5 for germline pathogenicity assessment.⁵ This variant has been reported in somatic cancers (COSMIC COSV58693372, n = 9) and is classified as Likely Oncogenic/Likely Loss-of-function by OncoKB, consistent with a deleterious biological effect.⁶