TONSL p.Arg294=
c.882G>A · rs139669876 · VCV1547921
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.068%, afr)
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 -0.42 | GERP -0.69 |
| Overall | ||
| CADD | 7.508 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.068%
African / African-American · 51/75,054 alleles
Filtering AF
0.0531%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0478%
Overall
0.00905%
146/1,612,826 alleles · ultra-rare
exomes 111/1,460,488 · genomes 35/152,338 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.068% | 1,472 |
| Middle Eastern | 0.0495% | 2,020 |
| Admixed American | 0.0283% | 3,531 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,620 |
| European (non-Finnish) | 0.00593% | 16,857 |
| South Asian | 0.0011% | 91,086 |
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.Arg294=
- Coding
- c.882G>A
- MANE Select
- NM_013432
- dbSNP
- rs139669876
- Type
- single nucleotide variant
- Location
- chr8:144441095 (GRCh38)
- Gene constraint
- LOEUF 1.024 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.06 · 3 PDB
- Residue 294
- 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.Arg294Leu Uncertain significance ★ ⚠ same residue
- TONSL p.Arg294Trp 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
- TONSL p.Glu487Lys 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-arg294 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown