Is FBXO7 c.122+116C>T pathogenic?

FBXO7 c.122+116C>T is classified Benign in FBXO7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-03-31). Common (popmax 21.9%, mid) — too common for a highly-penetrant pathogenic allele.

FBXO7 c.122+116C>T

Q: How common is FBXO7 c.122+116C>T in the general population?

FBXO7 c.122+116C>T is common (popmax 21.9%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs8136485 · VCV1256791

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 21.9%, mid) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +116	deep intronic (+116 nt into the intron)
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.5	GERP -2
Overall
CADD	6.824	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 21.9% Middle Eastern · 950/4,342 alleles

Filtering AF 21.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 21.1%

Overall 20.6% 315,318/1,532,754 alleles · common exomes 284,204/1,380,690 · genomes 31,114/152,064 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	25.6%	4
Finnishnot grpmax-eligible	21.9%	5
Middle Easterngrpmax	21.9%	5
European (non-Finnish)	21.2%	5
Admixed American	20.8%	5
Remaining individualsnot grpmax-eligible	20.4%	5
African / African-American	19.9%	5
East Asian	18.6%	5
Amishnot grpmax-eligible	13.1%	8
South Asian	11.5%	9

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Coding: c.122+116C>T
MANE Select: NM_012179
dbSNP: rs8136485
Type: single nucleotide variant
Location: chr22:32475240 (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

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-c-122-plus-116c-t (accessed [today's date]).

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