Is FLCN p.Ser79fs (c.235_238del) pathogenic?

FLCN p.Ser79fs (c.235238del) is classified Pathogenic in FLCN (ClinVar, Multiple submitters, 13 submitters; last evaluated 2025-05-02). Very rare (popmax 0.000254%, nfe); Associated with FLCN-related disorders.

What condition is associated with FLCN p.Ser79fs (c.235_238del)?

FLCN p.Ser79fs (c.235_238del) is associated with FLCN-related disorders, familial spontaneous pneumothorax, hereditary neoplastic syndrome (ClinVar).

How common is FLCN p.Ser79fs (c.235_238del) in the general population?

FLCN p.Ser79fs (c.235_238del) is very rare (popmax 0.000254%, nfe) (gnomAD).

FLCN p.Ser79fs

c.235_238del · rs750146811 · VCV3371

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

FLCN-related disorders

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 4 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.5, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,032 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,124 alleles · very rare exomes 3/1,461,796 · genomes 0/152,328 · 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.Ser79fs
Coding: c.235_238del
MANE Select: NM_144997
dbSNP: rs750146811
Type: Deletion
Location: chr17:17227900 (GRCh38)
Gene constraint: LOEUF 0.487 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.14 · 4 PDB
Residue 79: a UniProt-annotated variant site (in a sporadic colorectal carcinoma; somatic mutation); the 'disordered' region

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

Disease context

FLCN-related disorders

Also linked: familial spontaneous pneumothorax hereditary neoplastic syndrome Birt-Hogg-Dube syndrome Birt-Hogg-Dube syndrome 1

Similar variants

FLCN p.Ser79Ala Uncertain significance ★★ ⚠ same residue
FLCN p.Ser79Leu Uncertain significance ★★ ⚠ same residue
FLCN p.Ser79= Benign/Likely benign ★★ same residue
FLCN p.Ser79Pro Uncertain significance ★ ⚠ same residue
FLCN p.Ser79Trp Uncertain significance ★ same residue
FLCN p.Ser79Ter Pathogenic same residue
FLCN c.1301_1302del Pathogenic ★★ same condition
FLCN c.1301-7_1304del 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-ser79fs (accessed [today's date]).

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