PS1
No alternate nucleotide change producing the same p.Ala286Pro amino acid substitution was identified from the available evidence, so PS1 was not applied.
PS2
No confirmed de novo occurrence with parental relationship confirmation was identified for this variant, so PS2 was not applied.
PS3
No well-established functional study showing a damaging effect for p.Ala286Pro was identified in the available evidence, so PS3 was not applied.
PS4
The available evidence does not provide a case-control enrichment analysis or sufficient independent affected-case count for this variant, so PS4 was not applied.
PM1
Available hotspot review did not identify codon 286 as a statistically significant hotspot, so there is insufficient evidence that this variant lies in a well-established critical region without benign variation.
PM6
No assumed de novo occurrence without full parental confirmation was identified for this variant, so PM6 was not applied.
PP1
No segregation data were identified for this variant, so PP1 was not applied.
PP2
Available evidence does not establish a gene-level missense-specific constraint or a validated missense-prone mechanism at this residue sufficient to apply PP2.
PP3
Computational evidence is not strong enough to support a damaging prediction.
PP4
No patient phenotype, laboratory phenotype, or disease-specific clinical presentation data were provided for this variant, so PP4 was not applied.
PP5
Although this variant is present in ClinVar, the available record does not provide an independent reputable-source assertion that can be used here for PP5.
