Is FN1 p.Pro39= (c.117C>G) pathogenic?

FN1 p.Pro39= (c.117C>G) is classified Benign/Likely benign in FN1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-27). Rare (popmax 0.196%, afr); Associated with glomerulopathy with fibronectin deposits 2.

What condition is associated with FN1 p.Pro39= (c.117C>G)?

FN1 p.Pro39= (c.117C>G) is associated with glomerulopathy with fibronectin deposits 2, spondylometaphyseal dysplasia, 'corner fracture' type (ClinVar).

How common is FN1 p.Pro39= (c.117C>G) in the general population?

FN1 p.Pro39= (c.117C>G) is rare (popmax 0.196%, afr) (gnomAD).

How is Fibronectin glomerulopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

FN1 p.Pro39=

c.117C>G · rs148348956 · VCV793483

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.196%, afr)

Conditions

glomerulopathy with fibronectin deposits 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.66	GERP -3.6, phastCons 0.99
Overall
CADD	9.776	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.196% African / African-American · 147/75,036 alleles

Filtering AF 0.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.16%

Overall 0.00961% 155/1,613,398 alleles · rare exomes 85/1,461,126 · genomes 70/152,272 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.196%	510
Remaining individualsnot grpmax-eligible	0.008%	12,499
Admixed American	0.00333%	30,001
European (non-Finnish)	8.48e-05%	1,179,926

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: FN1
Protein: p.Pro39=
Coding: c.117C>G
MANE Select: NM_212482
dbSNP: rs148348956
Type: single nucleotide variant
Location: chr2:215435686 (GRCh38)
Gene constraint: LOEUF 0.404 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.23 · 66 PDB
Residue 39: the 'disordered' region

Full FN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

glomerulopathy with fibronectin deposits 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: spondylometaphyseal dysplasia, 'corner fracture' type

For Fibronectin glomerulopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

FN1 p.Cys123Arg Pathogenic/Likely pathogenic ★★ same condition
FN1 p.Cys225Trp Pathogenic/Likely pathogenic ★★ same condition
FN1 p.Cys231Trp Likely pathogenic ★★ same condition
FN1 p.Cys87Trp Pathogenic ★★ same condition
FN1 p.Tyr973Cys Pathogenic ★★ same condition
FN1 c.2122+4T>C Uncertain significance ★★ same condition
FN1 c.2299+3A>T Uncertain significance ★★ same condition
FN1 c.3517+1G>A Uncertain significance ★★ 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/fn1-p-pro39 (accessed [today's date]).

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