NM_004333.5:c.2107G>A (p.Glu703Lys) is a missense variant in BRAF exon 17, within the C-terminal lobe of the kinase domain but outside all VCEP-specified PM1 critical functional domains (P-loop AA 459-474, CR3 activation segment AA 594-627).¹ The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada, meeting PM2 at supporting strength under the RASopathy VCEP.² BRAF has a gnomAD missense Z-score >3.09, meeting PP2 at supporting strength, consistent with low tolerance for benign missense variation in this gene.³ The REVEL score of 0.579 does not meet the VCEP thresholds for PP3 (≥0.7) or BP4 (≤0.3), and SpliceAI predicts no splice impact (max delta 0.06). Computational evidence is indeterminate.⁴ No functional data exists for p.Glu703Lys in any VCEP-approved assay (BRAF Kinase, MEK Activation, ERK Activation); the variant is not listed in the SVI functional studies spreadsheet. OncoKB reports Unknown Oncogenic Effect.⁵ No same-codon pathogenic comparator exists at residue 703 (PM5), no de novo observations have been reported (PS2/PM6), no case-control or segregation data is available (PS4/PP1), and no prior pathogenic assertion for E703K exists (PS1).⁶ ClinVar reports a single submitter classifying the variant as Uncertain Significance (Variation ID 4856330, criteria provided, single submitter). PP5 and BP6 are not applicable under this VCEP.⁷ The only met criteria are PM2_Supporting and PP2_Supporting. No pathogenic criteria at moderate, strong, or very strong level are met. Under the RASopathy VCEP combination rules, this evidence is insufficient to classify the variant as Pathogenic or Likely Pathogenic, and insufficient benign evidence exists to classify as Benign or Likely Benign. The variant remains a Variant of Uncertain Significance.⁸