Is FBXO7 p.Arg345Gln (c.1034G>A) pathogenic?

FBXO7 p.Arg345Gln (c.1034G>A) is classified Uncertain significance in FBXO7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-14). AlphaMissense: ambiguous (0.3565); Ultra-rare (popmax 0.011%, sas); Associated with Inborn genetic diseases.

What condition is associated with FBXO7 p.Arg345Gln (c.1034G>A)?

FBXO7 p.Arg345Gln (c.1034G>A) is associated with Inborn genetic diseases (ClinVar).

How common is FBXO7 p.Arg345Gln (c.1034G>A) in the general population?

FBXO7 p.Arg345Gln (c.1034G>A) is ultra-rare (popmax 0.011%, sas) (gnomAD).

What do computational predictors say about FBXO7 p.Arg345Gln (c.1034G>A)?

AlphaMissense predicts ambiguous (score 0.3565) — an in-silico prediction, not a clinical call.

FBXO7 p.Arg345Gln

c.1034G>A · VCV4619824

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3565 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3565	ambiguous
REVEL	0.373	indeterminate
SaProt	LLR -8.38	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 24 kb · p 0.42 · regional, not allelic
Overall
CADD	33.0	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 0.011% South Asian · 10/91,088 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.00062% 10/1,614,016 alleles · ultra-rare exomes 9/1,461,862 · genomes 1/152,154 · 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.Arg345Gln
Coding: c.1034G>A
MANE Select: NM_012179
Type: single nucleotide variant
Location: chr22:32493171 (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 345: the f-box domain

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.Arg345Ter Pathogenic/Likely pathogenic ★★ 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-arg345gln (accessed [today's date]).

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