NM_004448.3:c.3582del (p.Glu1195SerfsTer3) is a frameshift deletion in exon 27 of ERBB2, the last exon, predicted to truncate 58 C-terminal residues without triggering nonsense-mediated decay.¹ Under the ClinGen SVI PVS1 framework (PMC6185798), the variant qualifies for PVS1 at moderate strength: a frameshift in the last exon where NMD is not predicted and the truncated region (<10% of the protein) does not contain a critical functional domain — the kinase domain remains intact.² The variant is absent from all population databases (gnomAD v2.1, v4.1, gnomAD-Canada), supporting PM2 at supporting strength.³ No functional studies, case-control data, de novo observations, cosegregation data, or ClinVar classifications are available for this variant. Computational splicing prediction (SpliceAI max delta = 0.00) is neutral.⁴ The combined evidence (PVS1_Moderate + PM2_Supporting) yields 1 moderate and 1 supporting criterion. Under generic ACMG/AMP 2015 combination rules, this does not meet the threshold for Likely Pathogenic (requires ≥1 moderate + ≥4 supporting, or ≥2 moderate + ≥2 supporting, among other combinations). The variant is classified as a Variant of Uncertain Significance (VUS).⁵ Human review is recommended: ERBB2 is a proto-oncogene where C-terminal truncations have been associated with gain-of-function in somatic contexts, and the evidence for germline ERBB2 loss-of-function as a disease mechanism is limited.⁶