Is FLCN p.Phe150= (c.450T>C) pathogenic?

FLCN p.Phe150= (c.450T>C) is classified Benign/Likely benign in FLCN (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-26). Rare (popmax 0.134%, eas); Associated with Potocki-Lupski syndrome.

What condition is associated with FLCN p.Phe150= (c.450T>C)?

FLCN p.Phe150= (c.450T>C) is associated with Potocki-Lupski syndrome, colorectal cancer, nonpapillary renal cell carcinoma (ClinVar).

How common is FLCN p.Phe150= (c.450T>C) in the general population?

FLCN p.Phe150= (c.450T>C) is rare (popmax 0.134%, eas) (gnomAD).

FLCN p.Phe150=

c.450T>C · rs200672897 · VCV241925

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.134%, eas)

Conditions

Potocki-Lupski syndrome

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 -0.33	GERP -1.4, phastCons 0.001
Overall
CADD	7.545	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.134% East Asian · 60/44,868 alleles

Filtering AF 0.107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0968%

Overall 0.00447% 72/1,612,426 alleles · rare exomes 64/1,460,052 · genomes 8/152,374 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.134%	748
Remaining individualsnot grpmax-eligible	0.016%	6,246
Admixed American	0.00167%	59,764
European (non-Finnish)	8.48e-05%	1,179,338

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.Phe150=
Coding: c.450T>C
MANE Select: NM_144997
dbSNP: rs200672897
Type: single nucleotide variant
Location: chr17:17224090 (GRCh38)
Gene constraint: LOEUF 0.487 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.14 · 4 PDB
Residue 150: the udenn flcn/smcr8-type domain; a β-strand

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

Disease context

Potocki-Lupski syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: colorectal cancer nonpapillary renal cell carcinoma familial spontaneous pneumothorax hereditary neoplastic syndrome Birt-Hogg-Dube syndrome Birt-Hogg-Dube syndrome 1

Similar variants

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
FLCN c.1176+1G>C Pathogenic/Likely pathogenic ★★ same condition
FLCN c.1176+1G>T Likely pathogenic ★★ same condition
FLCN c.1176+2T>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-phe150 (accessed [today's date]).

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