PS1
No evidence was identified showing that this amino acid change has already been established as pathogenic from a different nucleotide change.
PS2
No confirmed de novo occurrence with parental confirmation was identified for this variant.
PS3
No validated functional study demonstrating a damaging effect of this specific STK11 variant was identified.
PS4
This variant is present in ClinVar, but no proband count, case-control enrichment, or other case-level data sufficient to show increased prevalence in affected individuals was identified.
PM1
Available evidence does not place p.(Gln8Glu) in a statistically significant hotspot, and no critical STK11 functional region at residue 8 was identified from the reviewed sources.
PM5
No established pathogenic missense comparator at codon 8 was identified from the reviewed evidence.
PM6
No assumed de novo occurrence without full parental confirmation was identified for this variant.
PP1
No segregation data were identified for this variant in affected family members.
PP2
The reviewed evidence did not provide a gene-specific basis to apply PP2 for this missense variant.
PP3
Available computational evidence does not support a deleterious effect: SpliceAI predicts no significant splice impact with max delta score 0.00, REVEL is low at 0.032, and BayesDel is negative at -0.435498.
PP4
No patient-specific phenotype information was available to determine whether the clinical presentation is highly specific for STK11-related disease.
PP5
ClinVar reports this variant as uncertain significance rather than as a pathogenic or likely pathogenic variant from a reputable source.
