TOE1 p.Ala103=
c.309C>T · VCV3703196
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.02%, 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 0.096 | GERP -1.5, phastCons 0.91 |
| Overall | ||
| CADD | 7.842 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.02%
Admixed American · 12/59,932 alleles
Filtering AF
0.0115%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00899%
Overall
0.000991%
16/1,613,748 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.02% | 4,994 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,240 |
| African / African-American | 0.00134% | 74,898 |
| European (non-Finnish) | 8.48e-05% | 1,179,935 |
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.Ala103=
- Coding
- c.309C>T
- MANE Select
- NM_025077
- Type
- single nucleotide variant
- Location
- chr1:45341545 (GRCh38)
- Gene constraint
- LOEUF 1.225 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.16 · 1 PDB
- Residue 103
- a UniProt-annotated variant site (in pch7; reduced protein levels; decreased function in snrna 3'-end processing)
Similar variants
- TOE1 p.Ala103Thr Pathogenic/Likely pathogenic ⚠ same residue
- 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
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-ala103 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown