Is FBXO7 p.Gln388Ter (c.1162C>T) pathogenic?

FBXO7 p.Gln388Ter (c.1162C>T) is classified Likely pathogenic in FBXO7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-06). Very rare (popmax 8.73e-05%, nfe).

How common is FBXO7 p.Gln388Ter (c.1162C>T) in the general population?

FBXO7 p.Gln388Ter (c.1162C>T) is very rare (popmax 8.73e-05%, nfe) (gnomAD).

FBXO7 p.Gln388Ter

c.1162C>T · VCV3901538

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.73e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (8 of 9, 20 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	Δ0.27	acceptor loss · deltas
Pangolin	Δ0.20	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.7	GERP 1.5, phastCons 1
Overall
CADD	45.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.73e-05% European (non-Finnish) · 1/1,145,902 alleles

Overall 6.37e-05% 1/1,570,846 alleles · very rare exomes 1/1,418,904 · genomes 0/151,942 · 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.Gln388Ter
Coding: c.1162C>T
MANE Select: NM_012179
Type: single nucleotide variant
Location: chr22:32495510 (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 388: the 'important for interaction with cdk6' region

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

Similar variants

FBXO7 p.Arg321Ter Pathogenic/Likely pathogenic ★★ same type
FBXO7 p.Arg345Ter Pathogenic/Likely pathogenic ★★ same type
FBXO7 p.Arg381Ter Pathogenic/Likely pathogenic ★★ same type
FBXO7 p.Arg45Ter Pathogenic/Likely pathogenic ★★ same type
FBXO7 p.Arg498Ter Pathogenic ★★ same type
FBXO7 p.Gln237Ter Pathogenic/Likely pathogenic ★★ same type
FBXO7 p.Thr22Met Pathogenic/Likely pathogenic ★★ same type
FBXO7 p.Ala84Val Uncertain significance ★★ ⚠ same type

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-gln388ter (accessed [today's date]).

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