FXN p.Ser57=
c.171G>C · rs767221228 · VCV1256262
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
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 1.4 | GERP 0.076, phastCons 0.007 |
| Overall | ||
| CADD | 2.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,766 alleles
Overall
6.2e-05%
1/1,613,690 alleles · very rare
exomes 0/1,461,522 · genomes 1/152,168 · 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
- FXN
- Protein
- p.Ser57=
- Coding
- c.171G>C
- MANE Select
- NM_000144
- dbSNP
- rs767221228
- Type
- single nucleotide variant
- Location
- chr9:69046390 (GRCh38)
- Gene constraint
- LOEUF 0.809 · pLI 0.16 (gnomAD)
- Structure
- AlphaFold pLDDT 75.93 · 19 PDB
Similar variants
- FXN p.Ser57fs Pathogenic ★ same residue
- FXN p.Leu106Ser Pathogenic ★★ same type
- FXN p.Met1Ile Pathogenic ★★ same type
- FXN p.Arg43His Uncertain significance ★★ ⚠ same type
- FXN p.Gly138Arg Uncertain significance ★★ ⚠ same type
- FXN p.Leu24Phe Uncertain significance ★★ ⚠ same type
- FXN p.Leu33Val Uncertain significance ★★ ⚠ same type
- FXN p.Pro30Thr 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/fxn-p-ser57 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown