FN1 p.Pro647=
c.1941T>G · rs1304755474 · VCV2901319
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 -1.1 | GERP -3.6 |
| Overall | ||
| CADD | 3.992 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,020 alleles
Overall
6.2e-05%
1/1,613,710 alleles · very rare
exomes 1/1,461,368 · genomes 0/152,342 · joint denominator
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.Pro647=
- Coding
- c.1941T>G
- MANE Select
- NM_212482
- dbSNP
- rs1304755474
- Type
- single nucleotide variant
- Location
- chr2:215414837 (GRCh38)
- Gene constraint
- LOEUF 0.404 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 70.23 · 66 PDB
- Residue 647
- the fibronectin type-iii 1 domain; a β-strand
Similar variants
- FN1 p.Pro647Ser Uncertain significance ★★ ⚠ same residue
- FN1 p.Cys123Arg Pathogenic/Likely pathogenic ★★ same type
- FN1 p.Cys225Trp Pathogenic/Likely pathogenic ★★ same type
- FN1 p.Cys231Trp Likely pathogenic ★★ same type
- FN1 p.Cys87Trp Pathogenic ★★ same type
- FN1 p.Tyr973Cys Pathogenic ★★ same type
- FN1 c.2122+4T>C Uncertain significance ★★ same type
- FN1 c.2299+3A>T Uncertain significance ★★ same type
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-pro647 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown