Is FLCN p.Ile172= (c.516C>T) pathogenic?

FLCN p.Ile172= (c.516C>T) is classified Conflicting classifications of pathogenicity in FLCN (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-24). Absent from gnomAD v4.1; Associated with Birt-Hogg-Dube syndrome 1.

What condition is associated with FLCN p.Ile172= (c.516C>T)?

FLCN p.Ile172= (c.516C>T) is associated with Birt-Hogg-Dube syndrome 1, hereditary neoplastic syndrome, Birt-Hogg-Dube syndrome (ClinVar).

How common is FLCN p.Ile172= (c.516C>T) in the general population?

FLCN p.Ile172= (c.516C>T) is absent from gnomAD v4.1 (gnomAD).

FLCN p.Ile172=

c.516C>T · rs2047176639 · VCV1640148

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 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 5.2	GERP 0.89, phastCons 1
Overall
CADD	10.86	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.Ile172=
Coding: c.516C>T
MANE Select: NM_144997
dbSNP: rs2047176639
Type: single nucleotide variant
Location: chr17:17224024 (GRCh38)
Gene constraint: LOEUF 0.487 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.14 · 4 PDB
Residue 172: the udenn flcn/smcr8-type domain; a UniProt-annotated variant site (in psp); a β-strand

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.Ile172Val Uncertain significance ★★ ⚠ same residue
FLCN p.Ile172Phe Uncertain significance ★ ⚠ same residue
FLCN p.Ile172Ser 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-ile172 (accessed [today's date]).

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