Is FLCN p.Ser577fs (c.1728_1735del) pathogenic?

FLCN p.Ser577fs (c.17281735del) is classified Uncertain significance in FLCN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). Associated with hereditary neoplastic syndrome.

What condition is associated with FLCN p.Ser577fs (c.1728_1735del)?

FLCN p.Ser577fs (c.1728_1735del) is associated with hereditary neoplastic syndrome (ClinVar).

FLCN p.Ser577fs

c.1728_1735del · VCV4642995

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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	escapes	premature termination codon in the last exon (14 of 14) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.15	GERP -3.4, phastCons 0.01

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

Variant & gene context

Gene: FLCN
Protein: p.Ser577fs
Coding: c.1728_1735del
MANE Select: NM_144997
Type: Deletion
Location: chr17:17213660 (GRCh38)
Gene constraint: LOEUF 0.487 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.14 · 4 PDB
Residue 577: 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

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

Similar variants

FLCN p.Ser577Ala Uncertain significance ★★ ⚠ same residue
FLCN p.Ser577Phe Uncertain significance ★★ ⚠ same residue
FLCN p.Ser577Pro Conflicting classifications of pathogenicity ★ ⚠ 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

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-ser577fs (accessed [today's date]).

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