Is FBXO7 p.Val201Met (c.601G>A) pathogenic?

FBXO7 p.Val201Met (c.601G>A) is classified Likely benign in FBXO7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-10). AlphaMissense: ambiguous (0.3974); Rare (popmax 0.494%, afr); Associated with parkinsonian-pyramidal syndrome.

What condition is associated with FBXO7 p.Val201Met (c.601G>A)?

FBXO7 p.Val201Met (c.601G>A) is associated with parkinsonian-pyramidal syndrome (ClinVar).

How common is FBXO7 p.Val201Met (c.601G>A) in the general population?

FBXO7 p.Val201Met (c.601G>A) is rare (popmax 0.494%, afr) (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.Val201Met (c.601G>A)?

AlphaMissense predicts ambiguous (score 0.3974) — an in-silico prediction, not a clinical call.

FBXO7 p.Val201Met

c.601G>A · rs61730783 · VCV533897

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3974 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.494%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

parkinsonian-pyramidal syndrome

Computational evidence

Protein change
AlphaMissense	0.3974	ambiguous
REVEL	0.172	moderately benign-leaning
SaProt	LLR -11.60	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 0.8, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 24 kb · p 0.42 · regional, not allelic
Overall
CADD	24.4	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 0.494% African / African-American · 371/75,048 alleles

Filtering AF 0.453% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.437%

Overall 0.0253% 408/1,614,166 alleles · rare exomes 181/1,461,858 · genomes 227/152,308 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.494%	202
Admixed American	0.0217%	4,617
Remaining individualsnot grpmax-eligible	0.0192%	5,209
Middle Eastern	0.0165%	6,062
South Asian	0.0011%	91,084
European (non-Finnish)	0.000847%	118,002

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.Val201Met
Coding: c.601G>A
MANE Select: NM_012179
dbSNP: rs61730783
Type: single nucleotide variant
Location: chr22:32484080 (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 201: 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.Val201= 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
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-val201met (accessed [today's date]).

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