TOE1 p.Ala118=
c.354T>C · rs145706522 · VCV1627672
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0605%, 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 0.3 | GERP -0.21, phastCons 0.41 |
| Overall | ||
| CADD | 7.788 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0605%
European (non-Finnish) · 714/1,179,888 alleles
Filtering AF
0.0568%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0554%
Overall
0.0465%
751/1,613,996 alleles · ultra-rare
exomes 696/1,461,736 · genomes 55/152,260 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0605% | 1,653 |
| Remaining individualsnot grpmax-eligible | 0.04% | 2,500 |
| Admixed American | 0.00833% | 12,002 |
| African / African-American | 0.00666% | 15,006 |
| Finnishnot grpmax-eligible | 0.00312% | 32,013 |
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.Ala118=
- Coding
- c.354T>C
- MANE Select
- NM_025077
- dbSNP
- rs145706522
- Type
- single nucleotide variant
- Location
- chr1:45341969 (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-ala118 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown