FLNB p.Cys2154=
c.6462C>T · VCV3613222
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.366 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.28 | acceptor gain · deltas |
| Constraint at this position | ||
| Conservation | phyloP -7.3 | GERP -5.4 |
| Overall | ||
| CADD | 13.47 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,062 alleles
Filtering AF
0.00286%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00195%
Overall
0.0015%
22/1,461,868 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,062 |
| South Asian | 0.00659% | 15,182 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,835 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
| Finnishnot grpmax-eligible | 0.00156% | 64,028 |
| European (non-Finnish) | 0.000847% | 118,005 |
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
- Protein
- p.Cys2154=
- Coding
- c.6462C>T
- MANE Select
- NM_001457
- Type
- single nucleotide variant
- Location
- chr3:58153469 (GRCh38)
- Gene constraint
- LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 76.96 · 23 PDB
- Residue 2154
- a β-strand; the 'interaction with flna 1' region; the 'interaction with inppl1' region
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-p-cys2154 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown