TONSL p.Ser1048=
c.3144C>T · rs569596561 · VCV745161
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0129%, nfe)
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 -2.6 | GERP -3.3 |
| Overall | ||
| CADD | 3.542 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0129%
European (non-Finnish) · 148/1,148,624 alleles
Filtering AF
0.0112%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0105%
Overall
0.0102%
159/1,556,168 alleles · ultra-rare
exomes 142/1,403,846 · genomes 17/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0129% | 7,761 |
| Admixed American | 0.00564% | 17,746 |
| East Asian | 0.00457% | 21,886 |
| Remaining individualsnot grpmax-eligible | 0.00335% | 29,868 |
| African / African-American | 0.00272% | 36,756 |
| Finnishnot grpmax-eligible | 0.00164% | 61,124 |
| South Asian | 0.00119% | 83,792 |
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.Ser1048=
- Coding
- c.3144C>T
- MANE Select
- NM_013432
- dbSNP
- rs569596561
- Type
- single nucleotide variant
- Location
- chr8:144434221 (GRCh38)
- Gene constraint
- LOEUF 1.024 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.06 · 3 PDB
- Residue 1048
- 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 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
- TONSL c.2775+5G>T Uncertain significance ★★ same type
- TONSL p.Ala1053Ser 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/tonsl-p-ser1048 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown