FOXRED1 p.Pro281=
c.843T>C · rs2497193298 · VCV2693693
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000254%, nfe)
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 -4.4 | GERP -4.3 |
| Overall | ||
| CADD | 5.58 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000254%
European (non-Finnish) · 3/1,179,982 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000186%
3/1,612,798 alleles · very rare
exomes 3/1,460,748 · genomes 0/152,050 · 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
- FOXRED1
- Protein
- p.Pro281=
- Coding
- c.843T>C
- MANE Select
- NM_017547
- dbSNP
- rs2497193298
- Type
- single nucleotide variant
- Location
- chr11:126276091 (GRCh38)
- Gene constraint
- LOEUF 1.118 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 90.12
- Residue 281
- a UniProt-annotated variant site (in mc1dn19)
Similar variants
- FOXRED1 c.733+1G>A Pathogenic/Likely pathogenic ★★ same type
- FOXRED1 c.86-1G>A Pathogenic/Likely pathogenic ★★ same type
- FOXRED1 p.Arg352Trp Pathogenic ★★ ⚠ same type
- FOXRED1 p.Arg89Ter Likely pathogenic ★★ same type
- FOXRED1 p.Cys331Ter Pathogenic/Likely pathogenic ★★ same type
- FOXRED1 p.Gln232Ter Pathogenic ★★ same type
- FOXRED1 p.Gln368Ter Pathogenic/Likely pathogenic ★★ same type
- FOXRED1 p.Glu353Ter Pathogenic/Likely pathogenic ★★ 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/foxred1-p-pro281 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown