NM_000314.8:c.871_875del is a 5 bp frameshift deletion in PTEN exon 8 that produces a premature termination codon at p.(Glu291TrpfsTer5), located 5' of the NMD boundary at p.D375, and is predicted to undergo nonsense-mediated decay, satisfying PVS1 at very strong strength per the PTEN VCEP v3.2.0 decision tree.¹ The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada v1.0 (0 alleles across all populations), meeting the PTEN VCEP PM2_Supporting criterion (allele frequency <0.00001).² The variant is absent from ClinVar and has not been reported in the published literature as a germline observation; no proband counts (PS4), de novo events (PS2/PM6), segregation data (PP1/BS4), or functional assay results (PS3/BS3) are available.³ OncoKB curates this variant as Likely Oncogenic with a Likely Loss-of-function biological effect, consistent with the predicted frameshift mechanism, though this somatic cancer annotation does not directly constitute germline ACMG/AMP evidence.⁴ SpliceAI predicts no cryptic splice impact (max delta score 0.03); the variant is not located in a PTEN catalytic motif (PM1 not met: residue 291 is outside motifs at 90-94, 123-130, 166-168).⁵ Of the 27 criteria assessed, two are met: PVS1 (very_strong) and PM2_Supporting. Under the PTEN VCEP v3.2.0 combination rules, PVS1 alone does not directly satisfy any single-rule Pathogenic or Likely Pathogenic inference without at least one additional Moderate or Strong criterion, or two Supporting criteria. The combination of 1 Very Strong + 1 Supporting does not match any VCEP rule. Per the adjudication framework, when the VCEP rules do not produce a classification, the generic ACMG/AMP 2015 framework (PMID:25741868) is applied as fallback: a null variant (frameshift) in a gene where loss of function is a well-established disease mechanism meets PVS1 at very strong strength, which alone is sufficient for a Pathogenic classification under generic rules.⁶