FLNB p.His2598=
c.7794T>C · rs140318342 · VCV747567
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0217%, amr)
Conditions
1
connective tissue disorder
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 | GERP -4.3 |
| Overall | ||
| CADD | 3.227 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0217%
Admixed American · 13/60,026 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0101%
Overall
0.00322%
52/1,614,168 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0217% | 4,617 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,930 |
| African / African-American | 0.00533% | 18,760 |
| East Asian | 0.00446% | 22,444 |
| European (non-Finnish) | 0.00212% | 47,201 |
| South Asian | 0.0011% | 91,066 |
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.His2598=
- Coding
- c.7794T>C
- MANE Select
- NM_001457
- dbSNP
- rs140318342
- Type
- single nucleotide variant
- Location
- chr3:58170747 (GRCh38)
- Gene constraint
- LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 76.96 · 23 PDB
- Residue 2598
- a β-strand; the 'interaction with inppl1' region; the 'self-association site, tail' region; the 'interaction with flna 2' region
Similar variants
- FLNB p.Phe161Cys Likely pathogenic ★★ same condition
- FLNB p.Gly496Cys Uncertain significance ★★ ⚠ same condition
- FLNB p.Thr1003Met Uncertain significance ★★ ⚠ same condition
- FLNB p.Thr1579Ile Uncertain significance ★★ ⚠ same condition
- FLNB c.1611-4G>A Benign ★★ same condition
- FLNB c.292+8C>A Benign/Likely benign ★★ same condition
- FLNB c.4222+8A>G Benign/Likely benign ★★ same condition
- FLNB c.5426-10G>A Benign/Likely benign ★★ 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-his2598 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown