FLCN p.Asp99=
c.297T>C · rs1597613086 · VCV755665
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
Conditions
3
Birt-Hogg-Dube syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.77 | GERP -1.1, phastCons 0.99 |
| Overall | ||
| CADD | 8.099 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/91,086 alleles
Overall
0.000124%
2/1,614,192 alleles · very rare
exomes 2/1,461,894 · genomes 0/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0011% | 91,086 |
| European (non-Finnish) | 8.47e-05% | 1,180,038 |
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
- FLCN
- Protein
- p.Asp99=
- Coding
- c.297T>C
- MANE Select
- NM_144997
- dbSNP
- rs1597613086
- Type
- single nucleotide variant
- Location
- chr17:17226275 (GRCh38)
- Gene constraint
- LOEUF 0.487 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.14 · 4 PDB
- Residue 99
- the udenn flcn/smcr8-type domain; a β-strand
Similar variants
- FLCN p.Asp99Asn Uncertain significance ★★ ⚠ same residue
- FLCN p.Asp99Gly Uncertain significance ★ ⚠ same residue
- FLCN p.Asp99His Uncertain significance ★ ⚠ same residue
- FLCN p.Asp99fs Pathogenic ★★ same residue
- FLCN c.1062+1G>A Pathogenic ★★ same condition
- FLCN c.1062+2T>G Pathogenic ★★ same condition
- FLCN c.1063-1G>T Likely pathogenic ★★ same condition
- FLCN c.1063-2A>G Pathogenic/Likely pathogenic ★★ 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/flcn-p-asp99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown