FLNB p.Pro254=
c.762G>A · rs371715057 · VCV508835
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00801%, afr)
Conditions
1
FLNB-Related Spectrum Disorders
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 -4.8 | GERP -5.4 |
| Overall | ||
| CADD | 6.235 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00801%
African / African-American · 6/74,892 alleles
Filtering AF
0.00605%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00565%
Overall
0.00595%
96/1,613,956 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00801% | 12,482 |
| European (non-Finnish) | 0.00737% | 13,563 |
| Admixed American | 0.00333% | 29,993 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
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.Pro254=
- Coding
- c.762G>A
- MANE Select
- NM_001457
- dbSNP
- rs371715057
- Type
- single nucleotide variant
- Location
- chr3:58081751 (GRCh38)
- Gene constraint
- LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 76.96 · 23 PDB
- Residue 254
- an α-helix; the 'disordered' region
Disease context
FLNB-Related Spectrum Disorders
Similar variants
- FLNB p.Pro254Leu Uncertain significance ★★ ⚠ same residue
- FLNB p.Glu1661Lys Uncertain significance ★★ ⚠ same condition
- FLNB p.Glu78Gly Uncertain significance ★★ ⚠ same condition
- FLNB p.His1117Arg Uncertain significance ★★ ⚠ same condition
- FLNB p.Leu1440Pro Uncertain significance ★★ ⚠ same condition
- FLNB p.Pro396Ser Uncertain significance ★★ ⚠ same condition
- FLNB p.Ser1096Phe Uncertain significance ★★ ⚠ same condition
- FLNB p.Ser188Cys Uncertain significance ★★ ⚠ same condition
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-pro254 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown