TONSL p.Arg400=
c.1200C>T · rs147865138 · VCV2070445
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0503%, mid)
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 -5.5 | GERP -3.9 |
| Overall | ||
| CADD | 0.156 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0503%
Middle Eastern · 3/5,968 alleles
Filtering AF
0.0351%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0312%
Overall
0.00429%
69/1,607,830 alleles · ultra-rare
exomes 64/1,455,512 · genomes 5/152,318 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0503% | 1,989 |
| South Asian | 0.0462% | 2,165 |
| Admixed American | 0.015% | 6,648 |
| Remaining individualsnot grpmax-eligible | 0.00643% | 15,554 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,556 |
| Finnishnot grpmax-eligible | 0.00161% | 62,108 |
| European (non-Finnish) | 0.000765% | 130,738 |
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.Arg400=
- Coding
- c.1200C>T
- MANE Select
- NM_013432
- dbSNP
- rs147865138
- Type
- single nucleotide variant
- Location
- chr8:144440441 (GRCh38)
- Gene constraint
- LOEUF 1.024 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.06 · 3 PDB
- Residue 400
- 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.Arg400Cys Uncertain significance ★★ ⚠ same residue
- TONSL p.Arg400His 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-arg400 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown