Is FBXO7 p.Ser231= (c.693C>T) pathogenic?

FBXO7 p.Ser231= (c.693C>T) is classified Conflicting classifications of pathogenicity in FBXO7 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-06-01). Rare (popmax 0.548%, nfe); Associated with parkinsonian-pyramidal syndrome.

What condition is associated with FBXO7 p.Ser231= (c.693C>T)?

FBXO7 p.Ser231= (c.693C>T) is associated with parkinsonian-pyramidal syndrome (ClinVar).

How common is FBXO7 p.Ser231= (c.693C>T) in the general population?

FBXO7 p.Ser231= (c.693C>T) is rare (popmax 0.548%, nfe) (gnomAD).

How is Parkinsonian-pyramidal syndrome inherited?

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

FBXO7 p.Ser231=

c.693C>T · rs61752254 · VCV341312

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.548%, nfe)

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 -12	GERP -5
Overall
CADD	0.19	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.548% European (non-Finnish) · 6,470/1,180,010 alleles

Filtering AF 0.537% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.533%

Overall 0.441% 7,121/1,614,128 alleles · rare exomes 6,695/1,461,868 · genomes 426/152,260 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.548%	182
Remaining individualsnot grpmax-eligible	0.37%	271
Finnishnot grpmax-eligible	0.237%	421
South Asian	0.162%	615
African / African-American	0.0866%	1,155
Middle Eastern	0.0825%	1,212
Admixed American	0.0783%	1,277
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,801
East Asian	0.00223%	44,874

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
Protein: p.Ser231=
Coding: c.693C>T
MANE Select: NM_012179
dbSNP: rs61752254
Type: single nucleotide variant
Location: chr22:32485115 (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 231: 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.Ser231Asn Uncertain significance ★ ⚠ same residue
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

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-ser231 (accessed [today's date]).

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