TONSL p.Trp110Ter
c.329G>A · rs1002531030 · VCV638578
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
TONSL-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 4 of 26 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 1.5, phastCons 1 |
| Overall | ||
| CADD | 40.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- TONSL
- Protein
- p.Trp110Ter
- Coding
- c.329G>A
- MANE Select
- NM_013432
- dbSNP
- rs1002531030
- Type
- single nucleotide variant
- Location
- chr8:144443257 (GRCh38)
- Gene constraint
- LOEUF 1.024 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.06 · 3 PDB
- Residue 110
- a UniProt-annotated variant site (in semdsp; disease phenotype includes immunologic and hematologic abnormalities)
Disease context
TONSL-related disorder
Similar variants
- TONSL p.Arg875Ter Pathogenic/Likely pathogenic ★★ same condition
- TONSL p.Gln177Ter Pathogenic/Likely pathogenic ★★ same condition
- TONSL p.Arg382His Uncertain significance ★★ ⚠ same condition
- TONSL p.Glu199Lys Uncertain significance ★★ same condition
- TONSL c.3007-2A>C Likely pathogenic ★ same condition
- TONSL p.Gln88Ter Likely pathogenic ★ same condition
- TONSL c.866-1G>C Uncertain significance ★ same condition
- TONSL c.449-2A>C Likely pathogenic same condition
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-trp110ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown