PS1
No pathogenic or likely pathogenic variant causing the same amino-acid change, p.(Tyr235Phe), was identified in the reviewed evidence, so PS1 was not established.
PS2
No confirmed de novo occurrence with parental confirmation was identified for this variant, so PS2 could not be applied.
PS3
No well-established functional study demonstrating a damaging effect of this exact variant was identified, so PS3 was not applied.
PS4
No enrichment data, odds ratio, or multiple independent affected observations sufficient for PS4 were identified for this variant.
PM1
This variant has not been shown to lie in a well-established functional domain or statistically significant hotspot without benign variation.
PM6
No assumed de novo occurrence without full parentage confirmation was identified for this variant, so PM6 could not be applied.
PP1
No segregation data were identified for this variant, so PP1 could not be applied.
PP2
Available evidence did not establish a gene-specific basis to apply PP2 for this missense variant, so PP2 was not assessed.
PP3
SpliceAI predicts no significant splice impact for this variant (max delta score 0.01), but no REVEL or BayesDel score was available to assess the missense effect itself.
PP4
No phenotype information was provided that was sufficiently specific to NF1 to support PP4 for this variant.
