Is FBXO7 c.-184C>T pathogenic?

FBXO7 c.-184C>T is classified Benign in FBXO7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-08-21). Common (popmax 23%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with parkinsonian-pyramidal syndrome.

What condition is associated with FBXO7 c.-184C>T?

FBXO7 c.-184C>T is associated with parkinsonian-pyramidal syndrome (ClinVar).

How is Parkinsonian-pyramidal syndrome inherited?

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

FBXO7 c.-184C>T

Q: How common is FBXO7 c.-184C>T in the general population?

FBXO7 c.-184C>T is common (popmax 23%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs11538371 · VCV341302

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 23%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

parkinsonian-pyramidal syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.3	GERP -1.8
Non-coding constraint	Z 0.83	1 kb window · o/e 0.92 · regional · uncalibrated
Overall
CADD	5.161	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 23% European (non-Finnish) · 85,473/372,178 alleles

Filtering AF 22.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 22.8%

Overall 17.5% 108,873/622,726 alleles · common exomes 86,469/470,566 · genomes 22,404/152,160 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	23%	4
Amishnot grpmax-eligible	22%	5
Finnishnot grpmax-eligible	17.5%	6
Remaining individualsnot grpmax-eligible	16.9%	6
Ashkenazi Jewishnot grpmax-eligible	16.9%	6
Admixed American	11.3%	9
Middle Eastern	8.25%	12
South Asian	6.15%	16
African / African-American	3.97%	25
East Asian	0.0338%	2,959

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FBXO7
Coding: c.-184C>T
MANE Select: NM_012179
dbSNP: rs11538371
Type: single nucleotide variant
Location: chr22:32474819 (GRCh38)
Gene constraint: LOEUF 0.955 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 67.13 · 2 PDB

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.Arg321Ter Pathogenic/Likely pathogenic ★★ same condition
FBXO7 p.Arg345Ter Pathogenic/Likely pathogenic ★★ same condition
FBXO7 p.Arg381Ter Pathogenic/Likely pathogenic ★★ same condition
FBXO7 p.Arg45Ter Pathogenic/Likely pathogenic ★★ same condition
FBXO7 p.Arg498Ter Pathogenic ★★ same condition
FBXO7 p.Gln237Ter Pathogenic/Likely pathogenic ★★ same condition
FBXO7 p.Thr22Met Pathogenic/Likely pathogenic ★★ same condition
FBXO7 p.Ala84Val Uncertain significance ★★ ⚠ 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-c-minus-184c-t (accessed [today's date]).

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