NM_017763.5:c.1196C>T (p.Pro399Leu) is absent from gnomAD v2.1 (0/223,892 alleles) and v4.1 (0/1,595,338 alleles), meeting PM2 at supporting strength.¹ Multiple in silico tools predict a benign effect: REVEL score 0.022, BayesDel score -0.736863, and SpliceAI max delta 0.01 with no predicted splice impact, meeting BP4 at supporting benign strength.² The variant is reported in ClinVar as Uncertain Significance by a single clinical testing laboratory (VariationID 2093022) with review status 'criteria provided, single submitter.' This does not satisfy PP5 or BP6 thresholds.³ The variant is a missense substitution outside known null-variant buckets, so PVS1 is not applicable. No functional studies, segregation data, de novo observations, case-control evidence, or same-residue pathogenic comparators are available for this variant.⁴ Applying generic ACMG/AMP 2015 combination rules (PMID:25741868): one supporting pathogenic criterion (PM2) and one supporting benign criterion (BP4) are present. These are at equal weight and do not meet any pathogenic, likely pathogenic, benign, or likely benign combination threshold.⁵ Final classification: Uncertain Significance.