Is FBXO7 p.Ser247Phe (c.740C>T) pathogenic?

FBXO7 p.Ser247Phe (c.740C>T) is classified Uncertain significance in FBXO7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). AlphaMissense: likely benign (0.0867); Ultra-rare (popmax 0.0274%, sas); Associated with Inborn genetic diseases.

What condition is associated with FBXO7 p.Ser247Phe (c.740C>T)?

FBXO7 p.Ser247Phe (c.740C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FBXO7 p.Ser247Phe (c.740C>T) in the general population?

FBXO7 p.Ser247Phe (c.740C>T) is ultra-rare (popmax 0.0274%, sas) (gnomAD).

What do computational predictors say about FBXO7 p.Ser247Phe (c.740C>T)?

AlphaMissense predicts likely benign (score 0.0867) — an in-silico prediction, not a clinical call.

FBXO7 p.Ser247Phe

c.740C>T · VCV4256133

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0867 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0274%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0867	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -8.26	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 -0.77	GERP -0.49
Regional constraint	o/e 1.03	unconstrained · MANE · 24 kb · p 0.42 · regional, not allelic
Overall
CADD	5.304	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0274% South Asian · 25/91,080 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.00161% 26/1,614,152 alleles · ultra-rare exomes 25/1,461,838 · genomes 1/152,314 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0274%	3,643
European (non-Finnish)	8.47e-05%	1,180,004

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.Ser247Phe
Coding: c.740C>T
MANE Select: NM_012179
Type: single nucleotide variant
Location: chr22:32485162 (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 247: a β-strand; the 'important for dimerization and interaction with psmf1' 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.Ser247= 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-ser247phe (accessed [today's date]).

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