NM_001042492.2:c.3479G>A (p.Gly1160Asp) in NF1 is a missense variant absent from gnomAD population databases (v2.1, v4.1, Canada v1.0), satisfying PM2 at supporting strength.¹ This variant does not meet PVS1 criteria, as it is a missense variant and does not fall into the null-variant buckets (nonsense, frameshift, canonical splice) defined by the ClinGen SVI PVS1 recommendations (PMC6185798).² No variant-specific functional studies (PS3/BS3), segregation data (PP1/BS4), de novo observations (PS2/PM6), case-control prevalence (PS4), or same-residue pathogenic comparators (PM5/PS1) were identified in ClinVar or the literature.³ In silico predictions are conflicting: REVEL (0.851) supports a deleterious effect while BayesDel (0.15882) is in the benign range, and SpliceAI predicts no splice impact (max delta 0.06). These conflicting results preclude application of both PP3 and BP4.⁴ ClinVar classification is Likely pathogenic with review status 'criteria provided, single submitter' (2★); conflicting submissions exist (2 LP, 2 VUS, 1 P). PP5 does not apply at this review level and BP6 is not met as no benign classification exists.⁵ The NF1 CSPEC framework (ClinGen Neurofibromatosis and Schwannomatosis Expert Panel, Version 1.0) was retrieved but is incomplete (framework_complete=false, empty criteria). Generic ACMG/AMP 2015 combination rules (PMID:25741868) are applied for final classification.⁶ With only one supporting pathogenic criterion (PM2) met and no benign criteria, this variant does not reach the threshold for Likely Pathogenic or Likely Benign classification under generic ACMG/AMP 2015 rules. The variant is classified as a Variant of Uncertain Significance (VUS).⁷