Is FBXO7 p.Gly177Arg (c.529G>A) pathogenic?

FBXO7 p.Gly177Arg (c.529G>A) is classified Uncertain significance in FBXO7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-23). AlphaMissense: likely pathogenic (0.5885); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with FBXO7 p.Gly177Arg (c.529G>A)?

FBXO7 p.Gly177Arg (c.529G>A) is associated with Inborn genetic diseases (ClinVar).

How common is FBXO7 p.Gly177Arg (c.529G>A) in the general population?

FBXO7 p.Gly177Arg (c.529G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about FBXO7 p.Gly177Arg (c.529G>A)?

AlphaMissense predicts likely pathogenic (score 0.5885) — an in-silico prediction, not a clinical call.

FBXO7 p.Gly177Arg

c.529G>A · rs771557092 · VCV2488699

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5885 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5885	likely pathogenic
REVEL	0.764	pathogenic-leaning
SaProt	LLR -8.13	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 24 kb · p 0.42 · regional, not allelic
Overall
CADD	28.4	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 0.00167% Admixed American · 1/60,002 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,614,056 alleles · very rare exomes 2/1,461,856 · genomes 2/152,200 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,002
European (non-Finnish)	0.000254%	393,340

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.Gly177Arg
Coding: c.529G>A
MANE Select: NM_012179
dbSNP: rs771557092
Type: single nucleotide variant
Location: chr22:32484008 (GRCh38)
Gene constraint: LOEUF 0.955 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 67.13 · 2 PDB

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.Gly177= Likely benign ★ same residue
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

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-gly177arg (accessed [today's date]).

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