NM_004333.5:c.1447A>G (p.Lys483Glu) is a missense variant in BRAF, a gene where missense variants are a common mechanism of RASopathy disease. REVEL score of 0.973 strongly predicts a deleterious effect on protein function, satisfying PP3 at supporting strength. The gene's missense z-score exceeds 3.09 in gnomAD, meeting PP2 at supporting strength. The variant is present at extremely low frequency in gnomAD (1/251,326 alleles in v2.1; 1/1,613,408 alleles in v4.1) but is not absent, so PM2 (supporting) is not met under the VCEP requirement for complete absence. The variant lies outside VCEP-defined functional domains (P-loop AA 459-474, CR3 AA 594-627) and no pathogenic comparator exists at codon 483, so PM1 and PM5 are not met. No de novo, segregation, or case-control data are available for germline RASopathy. Functional data from the cancer literature classifies K483E as a Class 3 BRAF mutation (kinase-impaired, activates ERK via CRAF transactivation), but this has not been tested in VCEP-approved assays. No benign criteria are met. With two supporting pathogenic criteria (PP2, PP3) and no criteria at moderate or strong level, the variant does not meet any VCEP pathogenic or likely pathogenic classification rule. Per VCEP framework rules, the variant remains a Variant of Uncertain Significance.¹