FLNB c.2055+252G>A
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.25%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +252 | deep intronic (+252 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.1 | GERP -4.9 |
| Non-coding constraint | Z -0.37 | 1 kb window · o/e 1.04 · regional · uncalibrated |
| Overall | ||
| CADD | 2.509 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.25%
African / African-American · 518/41,552 alleles
Filtering AF
1.16%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.12%
Overall
0.366%
556/152,006 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.25% | 80 |
| Middle Eastern | 0.34% | 294 |
| Remaining individualsnot grpmax-eligible | 0.332% | 301 |
| Admixed American | 0.111% | 899 |
| European (non-Finnish) | 0.0192% | 5,221 |
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
- FLNB
- Coding
- c.2055+252G>A
- MANE Select
- NM_001457
- dbSNP
- rs116135152
- Type
- single nucleotide variant
- Location
- chr3:58108823 (GRCh38)
- Gene constraint
- LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 76.96 · 23 PDB
Similar variants
- FLNB c.4390+2T>C Pathogenic/Likely pathogenic ★★ same type
- FLNB c.5110-1G>A Likely pathogenic ★★ same type
- FLNB p.Arg1463Ter Pathogenic/Likely pathogenic ★★ same type
- FLNB p.Arg1948Ter Pathogenic ★★ same type
- FLNB p.Arg649Ter Pathogenic ★★ same type
- FLNB p.Asp167Gly Likely pathogenic ★★ ⚠ same type
- FLNB p.Glu227Lys Pathogenic ★★ same type
- FLNB p.Gly168Ser Pathogenic/Likely pathogenic ★★ ⚠ 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/flnb-c-2055-plus-252g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown