NM_002834.4:c.200G>A (p.Gly67Glu) in PTPN11 is absent from all population databases including gnomAD v2.1, v4.1, and gnomAD-Canada.¹ PTPN11 has a gnomAD missense z-score >3.09, indicating strong constraint against missense variation and supporting pathogenicity under PP2 at Supporting strength per RASopathy VCEP specifications.² REVEL in silico prediction score is 0.89, exceeding the VCEP threshold of 0.70 for PP3 at Supporting strength, consistent with a deleterious effect on protein function.³ The variant does not meet criteria for PS1 (no known pathogenic G67E), PM1 (position 67 is outside the VCEP-defined critical functional domain residue set), PM5 (no pathogenic comparators at codon 67), or any other pathogenic criterion above Supporting strength.⁴ With PM2_Supporting, PP2_Supporting, and PP3_Supporting met (three Supporting-level pathogenic criteria), the variant does not satisfy any Pathogenic or Likely Pathogenic combination rule in the RASopathy VCEP Version 2.3.0 framework. No Likely Pathogenic rule is triggered with fewer than four Supporting criteria in the absence of Moderate or Strong evidence. The variant is classified as a Variant of Uncertain Significance (VUS).⁵