TOE1 p.Ala87=
c.261C>T · rs148784816 · VCV1374161
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0214%, afr)
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 -5.6 | GERP -3.7 |
| Overall | ||
| CADD | 12.73 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0214%
African / African-American · 16/74,844 alleles
Filtering AF
0.0133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0109%
Overall
0.0106%
171/1,613,896 alleles · ultra-rare
exomes 145/1,461,876 · genomes 26/152,020 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0214% | 4,678 |
| European (non-Finnish) | 0.0124% | 8,082 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,496 |
| Admixed American | 0.005% | 19,995 |
| South Asian | 0.0011% | 91,076 |
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
- TOE1
- Protein
- p.Ala87=
- Coding
- c.261C>T
- MANE Select
- NM_025077
- dbSNP
- rs148784816
- Type
- single nucleotide variant
- Location
- chr1:45341497 (GRCh38)
- Gene constraint
- LOEUF 1.225 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.16 · 1 PDB
Similar variants
- MUTYH p.Trp12Ter Pathogenic/Likely pathogenic ★★ same type
- TOE1 p.Glu245Ter Pathogenic ★★ same type
- MUTYH c.36+5G>A Uncertain significance ★★ same type
- MUTYH p.Arg10His Uncertain significance ★★ ⚠ same type
- MUTYH p.Arg7Leu Uncertain significance ★★ ⚠ same type
- MUTYH p.Pro3Leu Uncertain significance ★★ ⚠ same type
- TOE1 p.Arg184Cys Uncertain significance ★★ ⚠ same type
- TOE1 p.Arg184His 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/toe1-p-ala87 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown