Is FBXO7 p.Tyr52Cys (c.155A>G) pathogenic?

FBXO7 p.Tyr52Cys (c.155A>G) is classified Likely benign in FBXO7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-08). AlphaMissense: likely benign (0.0683); Rare (popmax 0.343%, eas); Associated with parkinsonian-pyramidal syndrome.

What condition is associated with FBXO7 p.Tyr52Cys (c.155A>G)?

FBXO7 p.Tyr52Cys (c.155A>G) is associated with parkinsonian-pyramidal syndrome (ClinVar).

How common is FBXO7 p.Tyr52Cys (c.155A>G) in the general population?

FBXO7 p.Tyr52Cys (c.155A>G) is rare (popmax 0.343%, eas) (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.Tyr52Cys (c.155A>G)?

AlphaMissense predicts likely benign (score 0.0683) — an in-silico prediction, not a clinical call.

FBXO7 p.Tyr52Cys

c.155A>G · rs550610502 · VCV901597

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0683 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.343%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

parkinsonian-pyramidal syndrome

Computational evidence

Protein change
AlphaMissense	0.0683	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -6.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 1.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 24 kb · p 0.42 · regional, not allelic
Overall
CADD	23.2	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 0.343% East Asian · 154/44,884 alleles

Filtering AF 0.299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.282%

Overall 0.0141% 227/1,614,228 alleles · rare exomes 193/1,461,884 · genomes 34/152,344 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.343%	291
South Asian	0.0428%	2,336
Remaining individualsnot grpmax-eligible	0.024%	4,167
African / African-American	0.00533%	18,765
Admixed American	0.00333%	30,016
European (non-Finnish)	0.0011%	90,771

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.Tyr52Cys
Coding: c.155A>G
MANE Select: NM_012179
dbSNP: rs550610502
Type: single nucleotide variant
Location: chr22:32479013 (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 52: the 'ubiquitin-like' 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.Tyr52Ter Pathogenic ★ same residue
FBXO7 p.Tyr52= Likely benign ★ 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

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-tyr52cys (accessed [today's date]).

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