TONSL p.Arg1081=
c.3243G>A · rs200557916 · VCV1602143
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0384%, amr)
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 -0.51 | GERP -2.6, phastCons 0.032 |
| Overall | ||
| CADD | 4.591 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0384%
Admixed American · 23/59,936 alleles
Filtering AF
0.0262%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0222%
Overall
0.00192%
31/1,612,138 alleles · ultra-rare
exomes 29/1,459,804 · genomes 2/152,334 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0384% | 2,606 |
| East Asian | 0.00223% | 44,852 |
| European (non-Finnish) | 0.000593% | 168,505 |
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.Arg1081=
- Coding
- c.3243G>A
- MANE Select
- NM_013432
- dbSNP
- rs200557916
- Type
- single nucleotide variant
- Location
- chr8:144434122 (GRCh38)
- Gene constraint
- LOEUF 1.024 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.06 · 3 PDB
- Residue 1081
- a UniProt-annotated variant site (in semdsp; disease phenotype includes immunologic and hematologic abnormalities); a UniProt-annotated variant site (in semdsp); a UniProt-annotated variant site (in semdsp; disease phenotype includes primary aphakia and absent pupils)
Similar variants
- TONSL p.Arg1081Gln Uncertain significance ★ ⚠ same residue
- TONSL p.Arg1081Leu Uncertain significance ★ ⚠ same residue
- TONSL p.Arg1081Trp 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
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-arg1081 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown