TONSL p.Leu379=
c.1135C>T · rs140691873 · VCV1627882
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.81%, eas)
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 5.2 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 3.987 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.81%
East Asian · 814/44,886 alleles
Filtering AF
1.71%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.67%
Overall
0.0622%
1,003/1,612,870 alleles · low-frequency
exomes 879/1,460,534 · genomes 124/152,336 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 1.81% | 55 |
| Remaining individualsnot grpmax-eligible | 0.0864% | 1,157 |
| South Asian | 0.0768% | 1,301 |
| Admixed American | 0.02% | 5,002 |
| African / African-American | 0.0133% | 7,506 |
| European (non-Finnish) | 0.00364% | 27,441 |
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
- TONSL
- Protein
- p.Leu379=
- Coding
- c.1135C>T
- MANE Select
- NM_013432
- dbSNP
- rs140691873
- Type
- single nucleotide variant
- Location
- chr8:144440747 (GRCh38)
- Gene constraint
- LOEUF 1.024 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.06 · 3 PDB
- Residue 379
- a UniProt-annotated variant site (in semdsp; disease phenotype includes immunologic and hematologic abnormalities); a UniProt-annotated variant site (in semdsp)
Similar variants
- TONSL p.Leu379Arg Uncertain significance ★ ⚠ same residue
- TONSL p.Leu379Met Uncertain significance ★ same residue
- TONSL c.1891-1G>C Pathogenic/Likely pathogenic ★★ same type
- TONSL p.Arg875Ter Pathogenic/Likely pathogenic ★★ same type
- TONSL p.Arg934Trp Pathogenic ★★ ⚠ same type
- TONSL p.Gln177Ter Pathogenic/Likely pathogenic ★★ same type
- TONSL p.Gln511Ter Pathogenic/Likely pathogenic ★★ same type
- TONSL p.Glu487Lys 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/tonsl-p-leu379 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown