Is FN1 p.Arg83Pro (c.248G>C) pathogenic?

FN1 p.Arg83Pro (c.248G>C) is classified Uncertain significance in FN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-16). AlphaMissense: likely pathogenic (0.9153); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FN1 p.Arg83Pro (c.248G>C)?

FN1 p.Arg83Pro (c.248G>C) is associated with Inborn genetic diseases (ClinVar).

How common is FN1 p.Arg83Pro (c.248G>C) in the general population?

FN1 p.Arg83Pro (c.248G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FN1 p.Arg83Pro (c.248G>C)?

AlphaMissense predicts likely pathogenic (score 0.9153) — an in-silico prediction, not a clinical call.

FN1 p.Arg83Pro

c.248G>C · VCV4839932

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9153 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9153	likely pathogenic
REVEL	0.308	indeterminate
SaProt	LLR -8.32	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 28 kb · p 2.2e-08 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Arg83Pro
Coding: c.248G>C
MANE Select: NM_212482
Type: single nucleotide variant
Location: chr2:215434725 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FN1 p.Arg83= Likely benign ★★ same residue
FN1 p.Ala1127Gly Uncertain significance ★★ ⚠ same condition
FN1 p.Ala1184Val Uncertain significance ★★ ⚠ same condition
FN1 p.Ala1304Thr Uncertain significance ★★ ⚠ same condition
FN1 p.Ala1862Asp Uncertain significance ★★ ⚠ same condition
FN1 p.Ala1911Val Uncertain significance ★★ ⚠ same condition
FN1 p.Ala2257Pro Uncertain significance ★★ ⚠ same condition
FN1 p.Ala657Val 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-arg83pro (accessed [today's date]).

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