TONSL p.Gly486=
c.1458C>T · rs139005733 · VCV1540543
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.614%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.97 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.85 | gain · loss 0.66 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -3.9 | GERP -3.9 |
| Overall | ||
| CADD | 16.42 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.614%
African / African-American · 438/71,320 alleles
Filtering AF
0.567%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.548%
Overall
0.0334%
475/1,424,174 alleles · rare
exomes 207/1,271,840 · genomes 268/152,334 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.614% | 163 |
| Remaining individualsnot grpmax-eligible | 0.0267% | 3,748 |
| Admixed American | 0.0152% | 6,567 |
| South Asian | 0.00229% | 43,588 |
| European (non-Finnish) | 0.00109% | 91,703 |
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.Gly486=
- Coding
- c.1458C>T
- MANE Select
- NM_013432
- dbSNP
- rs139005733
- Type
- single nucleotide variant
- Location
- chr8:144440043 (GRCh38)
- Gene constraint
- LOEUF 1.024 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.06 · 3 PDB
- Residue 486
- the 'disordered' region; 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.Gly486Arg Uncertain significance ★ ⚠ same residue
- TONSL p.Gly486Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
- TONSL p.Gly486Val Benign ★ 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-gly486 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown