Is FLCN p.Pro472= (c.1416T>C) pathogenic?

FLCN p.Pro472= (c.1416T>C) is classified Benign/Likely benign in FLCN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-02). Very rare (popmax 0.0011%, sas); Associated with Birt-Hogg-Dube syndrome 1.

What condition is associated with FLCN p.Pro472= (c.1416T>C)?

FLCN p.Pro472= (c.1416T>C) is associated with Birt-Hogg-Dube syndrome 1, hereditary neoplastic syndrome, Birt-Hogg-Dube syndrome (ClinVar).

How common is FLCN p.Pro472= (c.1416T>C) in the general population?

FLCN p.Pro472= (c.1416T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

FLCN p.Pro472=

c.1416T>C · rs1420039293 · VCV530012

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

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 -5.8	GERP -3.6
Overall
CADD	0.625	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,096 alleles

Overall 0.000124% 2/1,614,068 alleles · very rare exomes 1/1,461,834 · genomes 1/152,234 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,096
European (non-Finnish)	8.47e-05%	1,180,044

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.Pro472=
Coding: c.1416T>C
MANE Select: NM_144997
dbSNP: rs1420039293
Type: single nucleotide variant
Location: chr17:17215201 (GRCh38)
Gene constraint: LOEUF 0.487 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.14 · 4 PDB
Residue 472: the cdenn flcn/smcr8-type domain; a UniProt-annotated variant site (in psp); a UniProt-annotated variant site (in bhd1)

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.Pro472Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
FLCN p.Pro472Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
FLCN p.Pro472Ser Uncertain significance ★ ⚠ 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-pro472 (accessed [today's date]).

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