Is FN1 p.Ser48= (c.144C>T) pathogenic?

FN1 p.Ser48= (c.144C>T) is classified Uncertain significance in FN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). Absent from gnomAD v4.1; Associated with glomerulopathy with fibronectin deposits 2.

What condition is associated with FN1 p.Ser48= (c.144C>T)?

FN1 p.Ser48= (c.144C>T) is associated with glomerulopathy with fibronectin deposits 2, spondylometaphyseal dysplasia, 'corner fracture' type (ClinVar).

How common is FN1 p.Ser48= (c.144C>T) in the general population?

FN1 p.Ser48= (c.144C>T) is absent from gnomAD v4.1 (gnomAD).

How is Fibronectin glomerulopathy inherited?

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

FN1 p.Ser48=

c.144C>T · VCV3585564

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

glomerulopathy with fibronectin deposits 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.95	donor gain · deltas
Pangolin	Δ0.44	gain · loss 0.20 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.9	GERP 0.94, phastCons 1
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FN1
Protein: p.Ser48=
Coding: c.144C>T
MANE Select: NM_212482
Type: single nucleotide variant
Location: chr2:215435659 (GRCh38)
Gene constraint: LOEUF 0.404 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.23 · 66 PDB
Residue 48: 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.Ser48Asn 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-ser48 (accessed [today's date]).

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