Is FLCN p.Ser331fs (c.989_990dup) pathogenic?

FLCN p.Ser331fs (c.989990dup) is classified Pathogenic in FLCN (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-07-01). No gnomAD frequency available for this variant; Associated with Birt-Hogg-Dube syndrome.

What condition is associated with FLCN p.Ser331fs (c.989_990dup)?

FLCN p.Ser331fs (c.989_990dup) is associated with Birt-Hogg-Dube syndrome (ClinVar).

How common is FLCN p.Ser331fs (c.989_990dup) in the general population?

FLCN p.Ser331fs (c.989_990dup) is no gnomAD frequency available for this variant (gnomAD).

FLCN p.Ser331fs

c.989_990dup · rs2544194629 · VCV2578507

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Birt-Hogg-Dube syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 9 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	GERP -1.4, phastCons 0.18

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FLCN
Protein: p.Ser331fs
Coding: c.989_990dup
MANE Select: NM_144997
dbSNP: rs2544194629
Type: Duplication
Location: chr17:17219090 (GRCh38)
Gene constraint: LOEUF 0.487 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.14 · 4 PDB
Residue 331: 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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FLCN p.Ser331del Uncertain significance ★★ same residue
FLCN p.Ser331Pro Uncertain significance ★★ ⚠ same residue
FLCN p.Ser331= Benign/Likely benign ★★ same residue
FLCN p.Ser331Cys Uncertain significance ★ ⚠ same residue
FLCN p.Ser331Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
FLCN p.Ser331Tyr Uncertain significance ★ ⚠ same residue
FLCN p.Ala310fs Pathogenic ★★ same condition
FLCN p.Ala412fs 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-ser331fs (accessed [today's date]).

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