Is FBXO7 p.Ser189fs (c.564_567del) pathogenic?

FBXO7 p.Ser189fs (c.564567del) is classified Pathogenic in FBXO7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-04). No gnomAD frequency available for this variant; Associated with parkinsonian-pyramidal syndrome.

What condition is associated with FBXO7 p.Ser189fs (c.564_567del)?

FBXO7 p.Ser189fs (c.564_567del) is associated with parkinsonian-pyramidal syndrome (ClinVar).

How common is FBXO7 p.Ser189fs (c.564_567del) in the general population?

FBXO7 p.Ser189fs (c.564_567del) is no gnomAD frequency available for this variant (gnomAD).

How is Parkinsonian-pyramidal syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

FBXO7 p.Ser189fs

c.564_567del · rs2544659247 · VCV2765341

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

parkinsonian-pyramidal syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.5	GERP 0.35, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FBXO7
Protein: p.Ser189fs
Coding: c.564_567del
MANE Select: NM_012179
dbSNP: rs2544659247
Type: Microsatellite
Location: chr22:32484039 (GRCh38)
Gene constraint: LOEUF 0.955 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 67.13 · 2 PDB
Residue 189: an α-helix; the 'important for dimerization and interaction with psmf1' region

Full FBXO7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

parkinsonian-pyramidal syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Parkinsonian-pyramidal syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult

Similar variants

FBXO7 p.Cys243fs Pathogenic/Likely pathogenic ★★ same condition
FBXO7 p.Tyr425fs Pathogenic/Likely pathogenic ★★ same condition
FBXO7 p.Arg306fs Pathogenic ★ same condition
FBXO7 p.Leu250fs Pathogenic ★ same condition
FBXO7 p.Val274fs Pathogenic ★ same condition
FBXO7 c.1181_1182+1del Uncertain significance ★ same condition
FBXO7 c.645+22_645+23del Likely benign ★ same condition
FBXO7 c.871+15_871+17del Likely benign ★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/fbxo7-p-ser189fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown