TOE1 p.Leu178=
c.534G>A · rs1002995018 · VCV2993145
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
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 2.8 | GERP 0.89, phastCons 1 |
| Overall | ||
| CADD | 7.545 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,898 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000248%
4/1,614,004 alleles · very rare
exomes 2/1,461,886 · genomes 2/152,118 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,898 |
| European (non-Finnish) | 0.000254% | 393,343 |
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.Leu178=
- Coding
- c.534G>A
- MANE Select
- NM_025077
- dbSNP
- rs1002995018
- Type
- single nucleotide variant
- Location
- chr1:45342425 (GRCh38)
- Gene constraint
- LOEUF 1.225 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.16 · 1 PDB
Similar variants
- TOE1 p.Leu178Arg Uncertain significance ★ ⚠ 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-leu178 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown