Is FBXO7 p.Asp361Gly (c.1082A>G) pathogenic?

FBXO7 p.Asp361Gly (c.1082A>G) is classified Likely benign in FBXO7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). AlphaMissense: ambiguous (0.4607); Ultra-rare (popmax 0.0846%, sas); Associated with parkinsonian-pyramidal syndrome.

What condition is associated with FBXO7 p.Asp361Gly (c.1082A>G)?

FBXO7 p.Asp361Gly (c.1082A>G) is associated with parkinsonian-pyramidal syndrome (ClinVar).

How common is FBXO7 p.Asp361Gly (c.1082A>G) in the general population?

FBXO7 p.Asp361Gly (c.1082A>G) is ultra-rare (popmax 0.0846%, sas) (gnomAD).

How is Parkinsonian-pyramidal syndrome inherited?

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

What do computational predictors say about FBXO7 p.Asp361Gly (c.1082A>G)?

AlphaMissense predicts ambiguous (score 0.4607) — an in-silico prediction, not a clinical call.

FBXO7 p.Asp361Gly

c.1082A>G · rs765132485 · VCV2195433

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4607 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0846%, sas)

Conditions

parkinsonian-pyramidal syndrome

Computational evidence

Protein change
AlphaMissense	0.4607	ambiguous
REVEL	0.308	indeterminate
SaProt	LLR -8.92	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 24 kb · p 0.42 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0846% South Asian · 77/91,070 alleles

Filtering AF 0.0693% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0637%

Overall 0.00576% 93/1,613,966 alleles · ultra-rare exomes 89/1,461,844 · genomes 4/152,122 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0846%	1,183
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0048%	20,835
European (non-Finnish)	0.00102%	98,331

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.Asp361Gly
Coding: c.1082A>G
MANE Select: NM_012179
dbSNP: rs765132485
Type: single nucleotide variant
Location: chr22:32493219 (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 361: the f-box domain

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

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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-p-asp361gly (accessed [today's date]).

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