TONSL p.Cys972=
c.2916C>T · rs369455058 · VCV1625370
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.437%, 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 -1.1 | GERP -3.3 |
| Overall | ||
| CADD | 11.33 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.437%
Middle Eastern · 25/5,718 alleles
Filtering AF
0.304%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.26%
Overall
0.0295%
472/1,598,844 alleles · rare
exomes 435/1,446,474 · genomes 37/152,370 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.437% | 229 |
| South Asian | 0.166% | 602 |
| Remaining individualsnot grpmax-eligible | 0.0421% | 2,377 |
| Admixed American | 0.0327% | 3,061 |
| European (non-Finnish) | 0.0211% | 4,732 |
| East Asian | 0.00453% | 22,064 |
| Finnishnot grpmax-eligible | 0.00326% | 30,709 |
| African / African-American | 0.00268% | 37,348 |
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.Cys972=
- Coding
- c.2916C>T
- MANE Select
- NM_013432
- dbSNP
- rs369455058
- Type
- single nucleotide variant
- Location
- chr8:144435107 (GRCh38)
- Gene constraint
- LOEUF 1.024 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.06 · 3 PDB
- Residue 972
- 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-cys972 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown