Is FLCN p.Pro359fs (c.1076del) pathogenic?

FLCN p.Pro359fs (c.1076del) is classified Pathogenic in FLCN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). Very rare (popmax 8.48e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with FLCN p.Pro359fs (c.1076del)?

FLCN p.Pro359fs (c.1076del) is associated with hereditary neoplastic syndrome (ClinVar).

How common is FLCN p.Pro359fs (c.1076del) in the general population?

FLCN p.Pro359fs (c.1076del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

FLCN p.Pro359fs

c.1076del · VCV3279036

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

hereditary neoplastic 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 10 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -8.9	GERP -4

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,534 alleles

Overall 6.2e-05% 1/1,613,488 alleles · very rare exomes 1/1,461,130 · genomes 0/152,358 · joint denominator

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.Pro359fs
Coding: c.1076del
MANE Select: NM_144997
Type: Deletion
Location: chr17:17217169 (GRCh38)
Gene constraint: LOEUF 0.487 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.14 · 4 PDB
Residue 359: the cdenn flcn/smcr8-type domain; a UniProt-annotated variant site (in psp); a UniProt-annotated variant site (in bhd1); an α-helix

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FLCN p.Pro359Leu Uncertain significance ★★ ⚠ same residue
FLCN p.Pro359Ser Uncertain significance ★★ ⚠ same residue
FLCN c.1301_1302del Pathogenic ★★ same condition
FLCN p.Ala64fs Pathogenic/Likely pathogenic ★★ same condition
FLCN p.Ala6fs Pathogenic ★★ same condition
FLCN p.Arg168fs Pathogenic ★★ same condition
FLCN p.Arg268_Leu269insTer Pathogenic ★★ same condition
FLCN p.Arg341fs 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-pro359fs (accessed [today's date]).

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