The PTEN c.525del (p.Tyr176IlefsTer7; p.Y176Ifs*7) variant has not been observed in COSMIC, has been reported in ClinVar as Pathogenic by one clinical laboratory, and is listed in OncoKB as Likely Oncogenic with a likely loss-of-function effect.¹ This variant is absent from gnomAD v2.1 and gnomAD v4.1, which is below the PTEN PM2 threshold of 0.00001 (0.001%) and supports PM2 at supporting strength.² This deletion causes a frameshift with premature termination at codon 176 and falls 5' of the PTEN-specific p.D375 (c.1121) PVS1 threshold in transcript NM_000314.8, supporting PVS1 as a loss-of-function variant in a gene where loss of function is an established disease mechanism.³ SpliceAI predicts no significant splice effect for this variant, with a maximum delta score of 0.02, so no separate computational splice criterion is added.⁴