FLNB p.Ala83=
c.249G>A · rs112750785 · VCV346299
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.98%, 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 0.24 | GERP -3.9, phastCons 0.95 |
| Overall | ||
| CADD | 10.98 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.98%
African / African-American · 1,487/75,050 alleles
Filtering AF
1.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.86%
Overall
0.106%
1,709/1,613,932 alleles · low-frequency
exomes 827/1,461,608 · genomes 882/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.98% | 50 |
| Admixed American | 0.138% | 723 |
| Remaining individualsnot grpmax-eligible | 0.128% | 781 |
| Middle Eastern | 0.066% | 1,515 |
| European (non-Finnish) | 0.00449% | 22,264 |
| Finnishnot grpmax-eligible | 0.00157% | 63,846 |
| South Asian | 0.0011% | 91,086 |
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.Ala83=
- Coding
- c.249G>A
- MANE Select
- NM_001457
- dbSNP
- rs112750785
- Type
- single nucleotide variant
- Location
- chr3:58008813 (GRCh38)
- Gene constraint
- LOEUF 0.504 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 76.96 · 23 PDB
- Residue 83
- the calponin-homology (ch) 1 domain; an α-helix; the 'actin-binding' region
Disease context
FLNB-Related Spectrum Disorders
Similar variants
- FLNB p.Ala83Ser 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-ala83 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown