Is FBXO7 p.Gly132Asp (c.395G>A) pathogenic?

FBXO7 p.Gly132Asp (c.395G>A) is classified Likely benign in FBXO7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.0557); Ultra-rare (popmax 0.0133%, afr); Associated with Inborn genetic diseases.

What condition is associated with FBXO7 p.Gly132Asp (c.395G>A)?

FBXO7 p.Gly132Asp (c.395G>A) is associated with Inborn genetic diseases (ClinVar).

How common is FBXO7 p.Gly132Asp (c.395G>A) in the general population?

FBXO7 p.Gly132Asp (c.395G>A) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

What do computational predictors say about FBXO7 p.Gly132Asp (c.395G>A)?

AlphaMissense predicts likely benign (score 0.0557) — an in-silico prediction, not a clinical call.

FBXO7 p.Gly132Asp

c.395G>A · VCV4023949

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0557 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0557	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -6.02	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 1.1	GERP -2, phastCons 0.012
Regional constraint	o/e 1.03	unconstrained · MANE · 24 kb · p 0.42 · regional, not allelic
Overall
CADD	6.247	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 0.0133% African / African-American · 10/74,910 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.00062% 10/1,614,028 alleles · ultra-rare exomes 5/1,461,890 · genomes 5/152,138 · joint denominator

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.Gly132Asp
Coding: c.395G>A
MANE Select: NM_012179
Type: single nucleotide variant
Location: chr22:32479253 (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 132: the 'disordered' region; the 'important for interaction with cdk6' region

Full FBXO7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FBXO7 p.Ala84Val Uncertain significance ★★ ⚠ same condition
FBXO7 p.Asn367Ser Uncertain significance ★★ ⚠ same condition
FBXO7 p.Glu218Lys Uncertain significance ★★ ⚠ same condition
FBXO7 p.Gly497Ala Uncertain significance ★★ ⚠ same condition
FBXO7 p.Leu280Pro Uncertain significance ★★ ⚠ same condition
FBXO7 p.Met239Val Uncertain significance ★★ ⚠ same condition
FBXO7 p.Ser463Leu Uncertain significance ★★ ⚠ same condition
FBXO7 p.Thr57Ala 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-gly132asp (accessed [today's date]).

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