NM_002524.5:c.182A>G (p.Gln61Arg) is a missense variant in exon 3 of NRAS affecting the critical Switch II domain (codon 61). This variant is absent from population databases (gnomAD v2.1, v4.1, gnomAD-Canada).¹ The p.Gln61Arg amino acid change is an established pathogenic variant at the analogous residue in HRAS and KRAS, satisfying PS1 at Strong strength per the RASopathy VCEP.² Functional studies approved by the RASopathy VCEP have characterized this variant across at least two independent assay platforms (RAS Activation, MEK Activation, ERK Activation, AKT Phosphorylation), supporting a gain-of-function mechanism consistent with RASopathy pathogenesis (PS3_Moderate).³ The variant lies within the Switch II domain (AA 57-64), a VCEP-approved critical functional domain, satisfying PM1 at Moderate strength. Residue Q61 is the key catalytic glutamine that positions the water molecule for GTP hydrolysis.⁴ Multiple alternative pathogenic residue changes at NRAS codon 61 (Q61K, Q61L, Q61H) are established in the literature, satisfying PM5 at Moderate strength per VCEP rules.⁵ The variant is absent from gnomAD population databases, meeting PM2 at Supporting strength (VCEP-downgraded).⁶ REVEL in silico prediction score of 0.888 exceeds the VCEP threshold of 0.7, supporting a deleterious effect (PP3).⁷ Applying the RASopathy VCEP combination rules: one Strong criterion (PS1) and at least two Moderate criteria (PS3 + PM1 + PM5) satisfy Rule 7 or Rule 6 for Pathogenic classification. Alternatively, one Strong plus one Moderate plus two Supporting criteria may satisfy other rules. The evidence combination is consistent with a Pathogenic classification.⁸