TONSL p.Arg620=
c.1858C>A · rs34978644 · VCV1601692
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.181%, 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 3.6 | GERP 1.5, phastCons 1 |
| Overall | ||
| CADD | 5.501 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.181%
African / African-American · 136/75,030 alleles
Filtering AF
0.156%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.147%
Overall
0.0104%
168/1,611,378 alleles · rare
exomes 71/1,459,084 · genomes 97/152,294 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.181% | 552 |
| Admixed American | 0.0317% | 3,158 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,679 |
| Middle Eastern | 0.0165% | 6,058 |
| European (non-Finnish) | 8.48e-05% | 1,179,846 |
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.Arg620=
- Coding
- c.1858C>A
- MANE Select
- NM_013432
- dbSNP
- rs34978644
- Type
- single nucleotide variant
- Location
- chr8:144436789 (GRCh38)
- Gene constraint
- LOEUF 1.024 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.06 · 3 PDB
- Residue 620
- 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.Arg620Trp Uncertain significance ★★ ⚠ same residue
- TONSL p.Arg620Gln Uncertain significance ★ ⚠ same residue
- TONSL p.Arg620Leu 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
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-arg620 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown