Is FLCN p.Ser243= (c.729G>A) pathogenic?

FLCN p.Ser243= (c.729G>A) is classified Benign/Likely benign in FLCN (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-08). Very rare (popmax 0.004%, afr); Associated with Birt-Hogg-Dube syndrome 1.

What condition is associated with FLCN p.Ser243= (c.729G>A)?

FLCN p.Ser243= (c.729G>A) is associated with Birt-Hogg-Dube syndrome 1, hereditary neoplastic syndrome, Birt-Hogg-Dube syndrome (ClinVar).

How common is FLCN p.Ser243= (c.729G>A) in the general population?

FLCN p.Ser243= (c.729G>A) is very rare (popmax 0.004%, afr) (gnomAD).

FLCN p.Ser243=

c.729G>A · rs377261933 · VCV485599

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

Birt-Hogg-Dube syndrome 1

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 0.2	GERP -3.8, phastCons 0.001
Overall
CADD	9.773	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,918 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000805% 13/1,614,078 alleles · very rare exomes 12/1,461,870 · genomes 1/152,208 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,973
East Asian	0.00223%	44,898
Admixed American	0.00167%	60,014
South Asian	0.0011%	91,094
European (non-Finnish)	0.000593%	168,577

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.Ser243=
Coding: c.729G>A
MANE Select: NM_144997
dbSNP: rs377261933
Type: single nucleotide variant
Location: chr17:17222551 (GRCh38)
Gene constraint: LOEUF 0.487 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.14 · 4 PDB
Residue 243: a UniProt-annotated variant site (in psp); a UniProt-annotated variant site (in bhd1); a turn

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

Disease context

Birt-Hogg-Dube syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome Birt-Hogg-Dube syndrome

Similar variants

FLCN p.Ser243Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-ser243 (accessed [today's date]).

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