Is FN1 p.Arg83= (c.247C>A) pathogenic?

FN1 p.Arg83= (c.247C>A) is classified Likely benign in FN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-24). Ultra-rare (popmax 0.0657%, mid); Associated with glomerulopathy with fibronectin deposits 2.

What condition is associated with FN1 p.Arg83= (c.247C>A)?

FN1 p.Arg83= (c.247C>A) is associated with glomerulopathy with fibronectin deposits 2, spondylometaphyseal dysplasia, 'corner fracture' type (ClinVar).

How common is FN1 p.Arg83= (c.247C>A) in the general population?

FN1 p.Arg83= (c.247C>A) is ultra-rare (popmax 0.0657%, mid) (gnomAD).

How is Fibronectin glomerulopathy inherited?

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

FN1 p.Arg83=

c.247C>A · rs780120577 · VCV1588068

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0657%, mid)

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 0.74	GERP -0.78, phastCons 1
Overall
CADD	11.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0657% Middle Eastern · 4/6,084 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00415% 67/1,613,972 alleles · ultra-rare exomes 62/1,461,862 · genomes 5/152,110 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0657%	1,521
Admixed American	0.015%	6,666
Remaining individualsnot grpmax-eligible	0.0128%	7,810
European (non-Finnish)	0.00373%	26,819
African / African-American	0.00267%	37,447

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.Arg83=
Coding: c.247C>A
MANE Select: NM_212482
dbSNP: rs780120577
Type: single nucleotide variant
Location: chr2:215434726 (GRCh38)
Gene constraint: LOEUF 0.404 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.23 · 66 PDB
Residue 83: a turn; the 'fibrin- and heparin-binding 1' region; the fibronectin type-i 1 domain

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.Arg83Pro Uncertain significance ★ ⚠ same residue
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

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-arg83 (accessed [today's date]).

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