Is FLCN p.Trp186Phe (c.557_558delinsTT) pathogenic?

FLCN p.Trp186Phe (c.557558delinsTT) is classified Uncertain significance in FLCN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-08). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with FLCN p.Trp186Phe (c.557_558delinsTT)?

FLCN p.Trp186Phe (c.557_558delinsTT) is associated with hereditary neoplastic syndrome (ClinVar).

How common is FLCN p.Trp186Phe (c.557_558delinsTT) in the general population?

FLCN p.Trp186Phe (c.557_558delinsTT) is no gnomAD frequency available for this variant (gnomAD).

FLCN p.Trp186Phe

c.557_558delinsTT · rs2544252641 · VCV2566324

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 14 kb · p 1.4e-05 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FLCN
Protein: p.Trp186Phe
Coding: c.557_558delinsTT
MANE Select: NM_144997
dbSNP: rs2544252641
Type: Indel
Location: chr17:17223982 (GRCh38)
Gene constraint: LOEUF 0.487 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.14 · 4 PDB
Residue 186: the udenn flcn/smcr8-type domain; a UniProt-annotated variant site (in psp); 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.Trp186Arg Uncertain significance ★ ⚠ same residue
FLCN p.Trp186Cys Uncertain significance ★ ⚠ same residue
FLCN p.Trp186Leu Uncertain significance ★ ⚠ same residue
FLCN p.Lys192fs Pathogenic ★★ same condition
FLCN p.Leu189_Leu190= Benign/Likely benign ★★ same condition
FLCN c.1301-7_1323delinsTGCTGTCATCGTGGAGGTGA Likely pathogenic ★ same condition
FLCN p.Asn492fs Pathogenic ★ same condition
FLCN p.Ile426fs 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-trp186phe (accessed [today's date]).

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