c.368A>G (p.His123Arg) is a missense variant in exon 5 of PTEN, within the phosphatase catalytic motif (residues 123-130).¹ The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada, meeting PM2_Supporting under PTEN VCEP rules.² His123 is located within the VCEP-defined catalytic motif, meeting PM1_Moderate.³ The variant has been classified as Pathogenic by the ClinGen PTEN Variant Curation Expert Panel (ClinVar SCV000863477, reviewed by expert panel).⁴ In the Mighell et al. 2018 (PMID:29706350) saturation mutagenesis phosphatase activity assay, H123R has a cumulative fitness score of -3.83 (High_conf = True), meeting the PTEN VCEP threshold for PS3_Moderate (Cum_score <= -1.11).⁵ The ClinGen PTEN VCEP applied PM6_Moderate, noting an assumed de novo occurrence (parentage unconfirmed) in a patient with Cowden syndrome (Nelen et al. 1999, PMID:10234502).⁶ Computational evidence supports pathogenicity: REVEL score 0.985 meets PP3_Supporting; PTEN's low rate of benign missense variation supports PP2_Supporting.⁷ The ClinGen PTEN VCEP classification as Pathogenic supports PP5_Supporting, applied per user directive to override VCEP Not Applicable when expert panel classification exists.⁸