NM_000455.4:c.539_571delinsTGGTAGGGTGGCACCTC is a frameshift variant predicted to cause p.(Gly180ValfsTer102) with a premature termination codon at residue 281, expected to trigger nonsense-mediated decay. Loss of function is an established disease mechanism for STK11 in Peutz-Jeghers syndrome.¹ The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada population databases, supporting its rarity in the general population.² The variant is absent from ClinVar and has not been reported in affected individuals, in somatic cancer databases (COSMIC), or in any of the five gene-level functional publications reviewed.³ No variant-specific functional studies, segregation data, de novo observations, or case-control data were identified. Five publications retrieved via OncoKB discuss STK11 function at the gene level but none include NM_000455.4:c.539_571delinsTGGTAGGGTGGCACCTC. Under the ClinGen SVI PVS1 decision framework (PMC6185798), a frameshift variant upstream of the last exon in a gene with an established loss-of-function disease mechanism qualifies for PVS1 at full strength.⁴