PS1
Not assessed: the variant is absent from ClinVar, and no comparator data on a pathogenic change producing the identical amino acid was available.
PS2
Not assessed: no proband phenotype, parental genotypes, parentage confirmation, or de novo testing result is available.
PS3
Not assessed: no validated functional or biochemical assay data (kinase activity, phosphorylation, proliferation) for p.Ala257Val was available.
PS4
Not assessed: no affected-case series or case-control dataset reports this exact FGFR4 variant.
PM1
Not met: cancerhotspots.org returned no significant-hotspot row for FGFR4 A257, and no residue-level functional-domain annotation places codon 257 in a critical domain.
PM3
Not assessed: no affected-proband observation, second variant, phase result, or recessive FGFR4 disease evidence is present.
PM5
Not assessed: no previously established pathogenic variant with a different amino acid substitution at residue 257 was identified.
PM6
Not assessed: no report identifies the variant as de novo without confirmed parentage.
PP1
Not assessed: no affected relatives, genotypes, phenotypes, or informative meioses are reported.
PP2
Not assessed: no missense-constraint metric (e.g., gnomAD Z-score) or established missense disease mechanism for FGFR4 was available.
PP3
Not met: REVEL score 0.396 falls in the gray zone (0.250-0.750), below the >0.750 PP3 supporting threshold.
PP4
Not assessed: no proband phenotype or phenotype-specificity evidence is supplied.
PP5
Not met: no exact-variant ClinVar record or expert-panel Pathogenic/Likely pathogenic assertion is present.
