FLNB p.Val2375=
c.7125T>C · rs143223509 · VCV2154052
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0226%, afr)
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 -14 | GERP -5.7 |
| Overall | ||
| CADD | 0.499 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0226%
African / African-American · 17/75,056 alleles
Filtering AF
0.0144%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0118%
Overall
0.00161%
26/1,614,212 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0226% | 4,415 |
| Middle Eastern | 0.0165% | 6,062 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
| European (non-Finnish) | 0.000508% | 196,673 |
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.Val2375=
- Coding
- c.7125T>C
- MANE Select
- NM_001457
- dbSNP
- rs143223509
- Type
- single nucleotide variant
- Location
- chr3:58163257 (GRCh38)
- Gene constraint
- LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 76.96 · 23 PDB
- Residue 2375
- a β-strand; the 'interaction with inppl1' region
Similar variants
- FLNB p.Val2375Ala Uncertain significance ★★ ⚠ same residue
- FLNB p.Val2375Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
- 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
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-val2375 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown