PS1
Not met: the reported p.N248K publication describes the same c.744C>G change, not a distinct nucleotide substitution producing the same amino acid.
PS2
Not assessed: no parental genotypes or maternity/paternity confirmation were available to establish de novo occurrence.
PS3
Not assessed: no functional assay tested p.Asn248Lys; the available publications provide only clinical screening or non-variant-specific context.
PS4
Not assessed: only one affected individual is reported, with no case-control comparison, cohort denominator, or statistical enrichment available.
PM1
Not assessed: the variant lies at residue 248, immediately outside the reported SDHB iron-sulfur domain boundary (B115-B247), with no approved hotspot designation.
PM3
Not assessed: the single reported case provides no second pathogenic SDHB variant, phase information, or recessive disease context.
PM5
Not assessed: no different pathogenic amino-acid substitution at residue 248 was identified, as the report concerns p.N248K itself.
PM6
Not assessed: no evidence states the variant was presumed de novo or provides a clinical basis for that presumption.
PP1
Not assessed: only one affected individual is documented, with no affected relatives, informative meioses, or cosegregation analysis.
PP2
Not assessed: SDHB loss of function is the established mechanism, and missense variation is not shown to be a common pathogenic mechanism for this gene.
PP4
Not assessed: the reported vagal head-and-neck paraganglioma does not establish phenotype specificity for SDHB-related disease, and no case phenotype data were provided.
PP5
Not met: the exact ClinVar record has three Likely pathogenic laboratory submissions but no expert-panel submission required for this criterion.