TONSL p.Ala397=
c.1191A>G · rs142838243 · VCV1663064
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.372%, 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 -15 | GERP -3.9 |
| Overall | ||
| CADD | 0.057 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.372%
African / African-American · 278/74,796 alleles
Filtering AF
0.336%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.322%
Overall
0.0242%
389/1,604,572 alleles · rare
exomes 225/1,452,392 · genomes 164/152,180 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.372% | 269 |
| Middle Eastern | 0.0838% | 1,193 |
| Admixed American | 0.0621% | 1,610 |
| Remaining individualsnot grpmax-eligible | 0.0323% | 3,100 |
| European (non-Finnish) | 0.00409% | 24,464 |
| South Asian | 0.0011% | 90,796 |
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.Ala397=
- Coding
- c.1191A>G
- MANE Select
- NM_013432
- dbSNP
- rs142838243
- Type
- single nucleotide variant
- Location
- chr8:144440450 (GRCh38)
- Gene constraint
- LOEUF 1.024 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.06 · 3 PDB
- Residue 397
- a UniProt-annotated variant site (in semdsp; disease phenotype includes immunologic and hematologic abnormalities); a UniProt-annotated variant site (in semdsp)
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-ala397 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown