FGB p.Pro48=
c.144C>G · VCV4968845
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0022%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.6 | GERP -4.3 |
| Overall | ||
| CADD | 4.938 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
European (non-Finnish) · 26/1,180,032 alleles
Filtering AF
0.00153%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0013%
Overall
0.00161%
26/1,614,052 alleles · very rare
exomes 25/1,461,862 · genomes 1/152,190 · 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
- FGB
- Protein
- p.Pro48=
- Coding
- c.144C>G
- MANE Select
- NM_005141
- Type
- single nucleotide variant
- Location
- chr4:154565837 (GRCh38)
- Gene constraint
- LOEUF 0.662 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 84.43 · 41 PDB
- Residue 48
- a UniProt-annotated variant site (in new york-1); the 'disordered' region
Similar variants
- FGB p.Arg44Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
- FGB p.Arg47Ter Pathogenic/Likely pathogenic ★★ same type
- FGB p.Arg199Cys Uncertain significance ★★ ⚠ same type
- FGB p.Arg199His Uncertain significance ★★ ⚠ same type
- FGB p.Arg224His Uncertain significance ★★ ⚠ same type
- FGB p.Arg395Gly Uncertain significance ★★ ⚠ same type
- FGB p.Arg47Gln Uncertain significance ★★ same type
- FGB p.Arg74Leu 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/fgb-p-pro48 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown