Is FN1 p.Asp381= (c.1143C>T) pathogenic?

FN1 p.Asp381= (c.1143C>T) is classified Benign/Likely benign in FN1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-21). Very rare (popmax 0.00822%, nfe); Associated with spondylometaphyseal dysplasia, 'corner fracture' type.

What condition is associated with FN1 p.Asp381= (c.1143C>T)?

FN1 p.Asp381= (c.1143C>T) is associated with spondylometaphyseal dysplasia, 'corner fracture' type, glomerulopathy with fibronectin deposits 2 (ClinVar).

How common is FN1 p.Asp381= (c.1143C>T) in the general population?

FN1 p.Asp381= (c.1143C>T) is very rare (popmax 0.00822%, nfe) (gnomAD).

FN1 p.Asp381=

Q: How is Spondylometaphyseal dysplasia, 'corner fracture' type inherited?

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

c.1143C>T · rs200307732 · VCV745070

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00822%, nfe)

Conditions

spondylometaphyseal dysplasia, 'corner fracture' type

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 -0.23	GERP -3.9, phastCons 0.001
Overall
CADD	9.486	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00822% European (non-Finnish) · 97/1,180,038 alleles

Filtering AF 0.00689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.01% 162/1,614,048 alleles · very rare exomes 129/1,461,868 · genomes 33/152,180 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0875%	1,143
European (non-Finnish)grpmax	0.00822%	12,165
African / African-American	0.00534%	18,731
Remaining individualsnot grpmax-eligible	0.0048%	20,827
Admixed American	0.00167%	60,002
South Asian	0.0011%	91,080

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp381=
Coding: c.1143C>T
MANE Select: NM_212482
dbSNP: rs200307732
Type: single nucleotide variant
Location: chr2:215424219 (GRCh38)
Gene constraint: LOEUF 0.404 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.23 · 66 PDB
Residue 381: the fibronectin type-ii 1 domain; a β-strand; the 'collagen-binding' region

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

Disease context

spondylometaphyseal dysplasia, 'corner fracture' type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: glomerulopathy with fibronectin deposits 2

For Spondylometaphyseal dysplasia, 'corner fracture' type (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood, Infancy, Neonatal

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-asp381 (accessed [today's date]).

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