PS1
Not met: no established pathogenic variant producing the same amino acid change (p.Ile417Phe) exists in ClinVar or the literature.
PS2
Not assessed: no proband, parental, or family genotype data were available, so a de novo occurrence could not be evaluated.
PS3
Not assessed: no variant-specific functional assay data (e.g., merlin localization or growth-suppression assays) were available.
PS4
Not assessed: no affected cases or case-control cohort data exist for this variant, so prevalence-based enrichment cannot be evaluated.
PM1
Not met: residue Ile417 shows no evidence of lying in a mutational hotspot or critical functional domain.
PM5
Not met: no different missense at codon 417 is established as pathogenic, and no same-residue candidates were found.
PM6
Not assessed: no observation of the variant arising de novo was available in any evidence source.
PP1
Not assessed: no family or pedigree data were available, so co-segregation could not be evaluated.
PP2
Not met: loss-of-function, not missense, is the established NF2 disease mechanism, and no missense constraint metric was collected.
PP3
Not met: REVEL 0.436 is below the 0.644 PP3 threshold, and SpliceAI max delta 0.02 predicts no splice impact.
PP4
Not assessed: no proband phenotype or family history was available, so phenotype specificity could not be evaluated.
PP5
Not met: ClinVar has no record of this variant, so no expert-panel pathogenic classification exists to support PP5.
