FLCN p.Lys342=
c.1026G>A · VCV3515614
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000678%, nfe)
Conditions
2
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 1 | GERP -3.1, phastCons 0.72 |
| Overall | ||
| CADD | 9.57 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000678%
European (non-Finnish) · 8/1,179,906 alleles
Filtering AF
0.000292%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000211%
Overall
0.000496%
8/1,613,710 alleles · very rare
exomes 8/1,461,394 · genomes 0/152,316 · joint denominator
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.Lys342=
- Coding
- c.1026G>A
- MANE Select
- NM_144997
- Type
- single nucleotide variant
- Location
- chr17:17219055 (GRCh38)
- Gene constraint
- LOEUF 0.487 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.14 · 4 PDB
- Residue 342
- the cdenn flcn/smcr8-type domain; a UniProt-annotated variant site (in psp); a UniProt-annotated variant site (in bhd1); a β-strand
Similar variants
- FLCN p.Lys342Glu Uncertain significance ★★ ⚠ same residue
- FLCN p.Lys342Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
- FLCN p.Lys342fs 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
- FLCN c.1176+1G>A 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-lys342 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown