NM_000314.8:c.638C>G (p.Pro213Arg) is absent from all queried population databases (gnomAD v2.1, v4.1, Canada), meeting PM2_Supporting per PTEN VCEP v3.2.0.¹ PP2_Supporting is applied: this is a missense variant in PTEN, a gene with a low rate of benign missense variation where missense variants are a common disease mechanism per PTEN VCEP.² PP3_Supporting is applied: REVEL score 0.868 exceeds the PTEN VCEP threshold of >0.7 for missense variants, supporting a deleterious computational prediction.³ PS3 was not met: the variant was not directly measured in the Mighell et al. 2018 phosphatase activity assay (Cum_score=NA), and the imputed score (−0.629) does not meet the PS3_Moderate threshold of ≤−1.11. No other variant-specific functional studies were identified.⁴ PM1 was not met: codon 213 lies outside the VCEP-defined catalytic motifs (residues 90-94, 123-130, 166-168). No statistically significant hotspot was identified at this residue.⁵ PVS1 is not applicable: the PTEN PVS1 decision tree is restricted to null variants (nonsense, frameshift, canonical splice site disruptions, exon deletions); missense substitutions are not within scope.⁶ Remaining pathogenic criteria (PS1, PS2, PS4, PS5, PM5, PM6, PP1, PP4, PP5) and benign criteria (BA1, BS1-BS4, BP1-BP7) are either not met, not assessed due to absent data, or not applicable per PTEN VCEP v3.2.0.⁷ Total evidence: PM2_Supporting + PP2_Supporting + PP3_Supporting. Per the PTEN VCEP classification rules (Richards et al. 2015 combination framework), this does not meet any pathogenic or likely pathogenic rule: Rule 4 requires one very strong criterion plus ≥2 supporting, which is not satisfied. The evidence is insufficient for classification beyond Variant of Uncertain Significance.⁸