NM_002834.4:c.169C>A (p.Gln57Lys) is a missense variant in PTPN11, a gene associated with autosomal dominant RASopathies. The variant is absent from gnomAD v2.1 and v4.1 population databases, satisfying PM2 at Supporting strength under the RASopathy VCEP v2.3.0.¹ REVEL in silico prediction score is 0.709, meeting the VCEP PP3 threshold of >=0.7 at Supporting strength.² PTPN11 has a missense z-score well above 3.09 in gnomAD, satisfying PP2 at Supporting strength under the VCEP rule.³ The variant is absent from ClinVar with no prior classifications, and no publications describe this specific variant.⁴ PM1 is not applicable: position 57 (Gln57) is adjacent to but not within the VCEP-defined functional domain residues (AA 58-63 are the closest listed range).⁵ No functional studies have tested p.Gln57Lys in any VCEP-approved assay (SHP-2 Phosphatase Activity, MEK Activation, ERK Activation).⁶ No de novo, segregation, proband-count, or case-control data are available for this variant. Under the RASopathy VCEP v2.3.0 classification rules, three Supporting-level pathogenic criteria (PM2_Supporting, PP2, PP3) are met. No Strong, Very Strong, Moderate, or Stand-Alone criteria are met on either the pathogenic or benign side.⁷ The VCEP classification framework requires at minimum either (a) one Strong criterion with >=2 Supportive, or (b) one Moderate criterion with >=4 Supportive, or (c) >=2 Moderate criteria to reach Likely Pathogenic. None of these thresholds are met. No benign criteria are triggered.⁸ Final classification: Variant of Uncertain Significance (VUS).