PS1
Not assessed: no ClinVar record of a different nucleotide substitution producing the same p.Pro3415Leu change has been classified pathogenic.
PS2
Not assessed: no proband or parental genotypes document a confirmed de novo occurrence of p.Pro3415Leu.
PS3
Not assessed: no functional assay data (e.g., methyltransferase activity) for this variant were available.
PS4
Not assessed: no affected carriers of this variant or case-control enrichment data were documented.
PM1
Not assessed: no significant hotspot at residue 3415 was found, and its location relative to known KMT2A functional domains could not be confirmed.
PM3
Not assessed: no evidence of this variant in trans with a pathogenic allele in an affected individual was available.
PM5
Not assessed: no pathogenic or likely pathogenic missense variant at residue 3415 with a different amino acid change was identified.
PM6
Not assessed: no de novo observation or parental-testing data are documented.
PP1
Not assessed: no relatives, genotypes, or informative meioses are reported, so cosegregation cannot be evaluated.
PP2
Not assessed: no missense constraint metric (e.g., gnomAD Z-score) was available to quantify benign missense tolerance in KMT2A.
PP3
Not met: REVEL 0.397 falls below the 0.644 PP3_Supporting threshold, and SpliceAI max delta 0.002 shows no splice impact.
PP4
Not assessed: no documented phenotype of a carrier establishes features highly specific for a KMT2A-related disorder.
PP5
Not met: the only ClinVar record is a single-laboratory uncertain-significance submission, not an expert-panel classification.
