NM_000314.8:c.745G>A (NP_000305.3:p.(Val249Met), p.(V249M)) is absent from gnomAD v2.1 and gnomAD v4.1, which is below the PTEN Expert Panel PM2 threshold of <0.00001 (0.001%) and supports PM2_Supporting.¹ As a PTEN missense variant, p.(Val249Met) supports PP2 because missense variation is an established disease mechanism for this gene in the PTEN Expert Panel framework.² In the Mighell PTEN phosphatase assay, p.Val249Met has a cumulative score of -0.30689816, which is above the PS3_Moderate threshold of <= -1.11 and below the BS3 threshold of >0, so the available PTEN-specific functional data do not support either PS3 or BS3.³ The REVEL score is 0.679, which is below the PTEN PP3 threshold of >0.7 and above the PTEN BP4 threshold of <0.5, so computational missense evidence does not support either criterion. With PM2_Supporting and PP2 met, and no additional PTEN Expert Panel pathogenic or benign criteria satisfied, PTEN p.(Val249Met) is classified as a variant of uncertain significance.⁴