Is FLCN p.Glu305= (c.915A>G) pathogenic?

FLCN p.Glu305= (c.915A>G) is classified Benign/Likely benign in FLCN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-08-31). Ultra-rare (popmax 0.0133%, amr); Associated with Birt-Hogg-Dube syndrome 1.

What condition is associated with FLCN p.Glu305= (c.915A>G)?

FLCN p.Glu305= (c.915A>G) is associated with Birt-Hogg-Dube syndrome 1, hereditary neoplastic syndrome, Birt-Hogg-Dube syndrome (ClinVar).

How common is FLCN p.Glu305= (c.915A>G) in the general population?

FLCN p.Glu305= (c.915A>G) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

FLCN p.Glu305=

c.915A>G · rs551034228 · VCV485604

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Conditions

Birt-Hogg-Dube syndrome 1

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 -0.46	GERP -3.4, phastCons 0.16
Overall
CADD	6.103	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/60,030 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.000743% 12/1,614,182 alleles · ultra-rare exomes 9/1,461,860 · genomes 3/152,322 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,504
African / African-American	0.00266%	37,525
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	8.47e-05%	1,180,043

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.Glu305=
Coding: c.915A>G
MANE Select: NM_144997
dbSNP: rs551034228
Type: single nucleotide variant
Location: chr17:17219166 (GRCh38)
Gene constraint: LOEUF 0.487 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.14 · 4 PDB
Residue 305: a UniProt-annotated variant site (in psp); a UniProt-annotated variant site (in bhd1); the 'disordered' region

Full FLCN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Birt-Hogg-Dube syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome Birt-Hogg-Dube syndrome

Similar variants

FLCN p.Glu305Lys Uncertain significance ★★ ⚠ same residue
FLCN p.Glu305fs 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
FLCN c.1176+1G>C 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-glu305 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown