Is FLCN p.Pro112= (c.336C>G) pathogenic?

FLCN p.Pro112= (c.336C>G) is classified Benign/Likely benign in FLCN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-22). Absent from gnomAD v4.1; Associated with Birt-Hogg-Dube syndrome 1.

What condition is associated with FLCN p.Pro112= (c.336C>G)?

FLCN p.Pro112= (c.336C>G) is associated with Birt-Hogg-Dube syndrome 1, hereditary neoplastic syndrome (ClinVar).

How common is FLCN p.Pro112= (c.336C>G) in the general population?

FLCN p.Pro112= (c.336C>G) is absent from gnomAD v4.1 (gnomAD).

FLCN p.Pro112=

c.336C>G · rs1457428918 · VCV3229245

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 2.7	GERP -0.54, phastCons 1
Overall
CADD	10.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FLCN
Protein: p.Pro112=
Coding: c.336C>G
MANE Select: NM_144997
dbSNP: rs1457428918
Type: single nucleotide variant
Location: chr17:17226236 (GRCh38)
Gene constraint: LOEUF 0.487 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.14 · 4 PDB
Residue 112: the udenn flcn/smcr8-type domain

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

Similar variants

FLCN p.Pro112Ala Uncertain significance ★★ ⚠ same residue
FLCN p.Pro112Leu Uncertain significance ★ ⚠ same residue
FLCN p.Pro112Ser Uncertain significance ★ ⚠ same residue
FLCN c.1062+1G>A Pathogenic ★★ same condition
FLCN c.1062+2T>G 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-pro112 (accessed [today's date]).

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