NM_000535.7:c.2380C>T (p.Pro794Ser) is a missense variant in exon 14 of PMS2. This variant is extremely rare in population databases: gnomAD v4.1 grpmax filtering allele frequency is 3.67e-06 (5/1,604,584 alleles), meeting the VCEP PM2_Supporting threshold of <0.00002.¹ The HCI prior probability for pathogenicity is 0.8253, exceeding the VCEP PP3_Moderate threshold of >0.81, supporting a deleterious computational prediction.² No functional studies, segregation data, tumor pathology data, or de novo observations are available for this variant. The variant is absent from COSMIC and OncoKB reports no variant-specific functional evidence.³ In ClinVar, this variant is classified as Uncertain Significance by 12 clinical laboratories and as Benign by 1 laboratory (ClinVar ID 220740), with no expert panel classification.⁴ Applying the ClinGen InSiGHT PMS2 VCEP v2.0.0 combining criteria: PM2_Supporting (1 point) and PP3_Moderate (2 points) are met. These do not reach any pathogenic classification tier (requires ≥1 Strong or ≥3 Moderate for Likely Pathogenic, or ≥2 Supporting for Likely Benign). The variant remains a Variant of Uncertain Significance.⁵