FGB p.Val28=
c.84T>A · rs375340782 · VCV702688
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0421%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.2 | GERP 0.35, phastCons 1 |
| Overall | ||
| CADD | 5.333 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0421%
African / African-American · 31/73,650 alleles
Filtering AF
0.0305%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0265%
Overall
0.00224%
35/1,564,684 alleles · ultra-rare
exomes 14/1,412,812 · genomes 21/151,872 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0421% | 2,376 |
| Remaining individualsnot grpmax-eligible | 0.00331% | 30,210 |
| Admixed American | 0.00181% | 55,222 |
| South Asian | 0.00117% | 85,526 |
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.Val28=
- Coding
- c.84T>A
- MANE Select
- NM_005141
- dbSNP
- rs375340782
- Type
- single nucleotide variant
- Location
- chr4:154563102 (GRCh38)
- Gene constraint
- LOEUF 0.662 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 84.43 · 41 PDB
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-val28 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown