NM_000077.4:c.9_32del (p.Ala4_Pro11del) is an in-frame 24-bp deletion removing 8 amino acids from the N-terminus of p16 in CDKN2A.¹ This deletion does not qualify as a null variant under the ClinGen SVI PVS1 framework (PMC6185798) and PVS1 is not applicable.² The variant is present in gnomAD v2.1 at 36/265,240 alleles (AF=0.0136%) and in gnomAD v4.1 at 153/1,606,464 alleles (AF=0.0095%) including one homozygote. These population frequencies are inconsistent with a high-penetrance pathogenic variant in a dominant cancer predisposition gene.³ One homozygote is observed in gnomAD v4.1 (BS2_supporting). Homozygosity for a pathogenic CDKN2A variant would be expected to produce a severe phenotype, and its presence in a population database argues against high penetrance pathogenicity.⁴ Functional studies demonstrate no damaging effect on p16 function. The N-terminal domain outside the ankyrin repeats is dispensable (PMID:8668202), and the specific 24-bp deletion mutant shows normal CDK4 binding (PMID:11159196) (BS3_supporting).⁵ The deletion occurs within a repetitive sequence region of CDKN2A exon 1 with 25 possible deletion variants yielding the same sequence alteration; both deletions and duplications have been documented at this site (BP3_supporting).⁶ SpliceAI predicts no significant splicing impact (max delta score = 0.06) (BP4_supporting).⁷ The variant has been observed in melanoma-affected families (PMID:10070944, PMID:16905682, PMID:25780468) and is reported as a variant of uncertain significance by 13 clinical laboratories in ClinVar, with one laboratory classifying it as likely benign. No expert panel has adjudicated this variant.⁸ Applying generic ACMG/AMP 2015 combination rules (PMID:25741868): the criteria met are BS2_supporting, BS3_supporting, BP3_supporting, and BP4_supporting. Four supporting benign criteria would satisfy 'Likely Benign' classification (≥2 supporting benign). However, the presence of a homozygous individual in gnomAD, taken together with functional evidence of normal protein activity and location in a repetitive region, supports a classification of Likely Benign.⁹