PS1
Not assessed: no validated pathogenic report of a different nucleotide change producing p.Thr5Pro was available.
PS2
Not assessed: no proband-specific de novo observation or parental testing was documented.
PS3
Not assessed: no variant-specific functional assay demonstrating a damaging effect was available.
PS4
Not assessed: no affected-case series, case-control comparison, or enrichment data for this variant was available.
PM1
Not met: no statistically significant cancer hotspot or RB1 domain evidence establishes residue 5 as a critical functional region.
PM2
Not met: the variant is present in gnomAD v4.1 (59/1,497,328 alleles), so it is not absent from population databases.
PM3
Not assessed: no observation places this variant in trans with a pathogenic variant.
PM5
Not assessed: no validated pathogenic missense comparator at RB1 codon 5 was available.
PM6
Not assessed: no suspected de novo occurrence without confirmed parentage was documented.
PP1
Not assessed: no family genotypes, informative meioses, or cosegregation results were available.
PP2
Not assessed: no gene-level analysis showing that benign RB1 missense variation is uncommon and disease-causing variants are predominantly missense.
PP3
Not met: REVEL score 0.127 falls below the PP3 threshold and in the benign-supporting range.
PP4
Not assessed: no proband phenotype or clinical information linking the variant to an RB1-related disorder was available.
PP5
Not met: ClinVar holds no expert-panel Pathogenic or Likely pathogenic assertion for this exact variant.
