PS1
Not assessed: no other pathogenic variant producing the same p.Val547Ile change exists, as this variant is absent from ClinVar.
PS2
Not assessed: no de novo occurrence was documented, with no parental testing showing the variant absent in both biological parents.
PS3
Not assessed: no functional assay data for p.Val547Ile (e.g., NRF2/ARE reporter activity) were available.
PS4
Not assessed: no case series, case-control comparison, or disease-enrichment data for this variant were available.
PM1
Not met: cancerhotspots.org reports no significant hotspot at residue 547, and COSMIC shows only a single somatic occurrence.
PM3
Not assessed: no observation of the variant in trans with a pathogenic variant in an affected individual was available.
PM5
Not assessed: no different missense change at residue 547 previously established as pathogenic was available for comparison.
PM6
Not assessed: no suspected de novo occurrence, with or without parental confirmation, was documented.
PP1
Not assessed: no family segregation data were available to evaluate cosegregation with disease.
PP2
Not assessed: no gene-level missense constraint metric (e.g., gnomAD missense Z-score) was available to establish PP2 eligibility.
PP3
Not met: REVEL score 0.271 is below the >=0.644 supporting-pathogenic threshold, and SpliceAI max delta 0.003 is below 0.2.
PP4
Not assessed: no patient phenotype or clinical presentation was provided.
PP5
Not met: the variant is absent from ClinVar, so no expert-panel pathogenic assertion exists to trigger PP5.
