PS1
Not assessed: no established pathogenic p.Phe459Ile comparator was identified, and ClinVar returned no record for c.1375T>A.
PS2
Not assessed: no parental genotypes or confirmed absence of c.1375T>A in both parents are documented for de novo evaluation.
PS3
Not assessed: No variant-specific functional assay, validated controls, or quantitative activity result was available for MBD4 p.Phe459Ile.
PS4
Not assessed: no affected-carrier, control-comparison, or case-control enrichment data are available for this variant.
PM1
Not assessed: no authoritative MBD4 domain table covered residue F459, and the hotspot search returned no statistically significant hotspot.
PM3
Not assessed: no affected-proband observation, second pathogenic allele, phase result, or inheritance data is available for MBD4 p.Phe459Ile.
PM5
Not assessed: zero eligible pathogenic or likely pathogenic alternate missense comparators were identified at MBD4 residue 459.
PM6
Not assessed: no reported suspected de novo occurrence with phenotype and proband evidence is available when parental testing is absent.
PP1
Not assessed: no informative affected-relative segregation, unaffected-relative testing, meioses, or phenotype concordance is documented.
PP2
Not met: available MBD4 evidence supports loss of function, not the required predominantly missense disease mechanism with uncommon benign missense variation.
PP4
Not assessed: no individual-level phenotype or highly specific clinical diagnosis is supplied for the variant carrier.
PP5
Not met: ClinVar reports no exact-variant result, so no expert-panel Pathogenic or Likely pathogenic assertion supports PP5.
