FIBP p.Leu321=
c.963G>A · rs370619260 · VCV3048041
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0202%, nfe)
Conditions
1
FIBP-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.015 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 0.61 | GERP -1.4, phastCons 1 |
| Overall | ||
| CADD | 9.237 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0202%
European (non-Finnish) · 238/1,180,036 alleles
Filtering AF
0.018%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0172%
Overall
0.0153%
247/1,614,036 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0202% | 4,958 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,414 |
| African / African-American | 0.004% | 24,971 |
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
- FIBP
- Protein
- p.Leu321=
- Coding
- c.963G>A
- MANE Select
- NM_004214
- dbSNP
- rs370619260
- Type
- single nucleotide variant
- Location
- chr11:65884433 (GRCh38)
- Gene constraint
- LOEUF 1.009 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.33
Disease context
FIBP-related disorder
Similar variants
- FIBP c.513-1G>C Likely pathogenic same condition
- FIBP p.Tyr173Ter Uncertain significance same condition
- FIBP p.Asp223Gly Uncertain significance ★★ same type
- FIBP p.Leu352Arg Uncertain significance ★★ ⚠ same type
- FIBP c.1004+33T>C Benign ★★ same type
- FIBP p.Ala50= Benign ★★ same type
- FIBP p.Gly187= Likely benign ★★ same type
- FIBP p.Gly263= Likely benign ★★ 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/fibp-p-leu321 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown