TYROBP p.Ile46=
c.138C>T · VCV4759715
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
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 -2.7 | GERP -3.7 |
| Overall | ||
| CADD | 1.969 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,892 alleles
Filtering AF
0.000953%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000787%
Overall
0.00124%
20/1,613,914 alleles · very rare
exomes 19/1,461,788 · genomes 1/152,126 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,892 |
| European (non-Finnish) | 0.00153% | 65,557 |
| South Asian | 0.0011% | 91,080 |
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
- TYROBP
- Protein
- p.Ile46=
- Coding
- c.138C>T
- MANE Select
- NM_003332
- Type
- single nucleotide variant
- Location
- chr19:35907537 (GRCh38)
- Gene constraint
- LOEUF 1.274 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 64.10 · 5 PDB
- Residue 46
- an α-helix
Similar variants
- TYROBP p.Ile46Met Uncertain significance ★ same residue
- TYROBP p.Ala44Thr Uncertain significance ★★ ⚠ same type
- TYROBP p.Arg70Trp Uncertain significance ★★ ⚠ same type
- TYROBP p.Asp104Asn Uncertain significance ★★ ⚠ same type
- TYROBP p.Asp32Asn Uncertain significance ★★ ⚠ same type
- TYROBP p.Pro40Leu Uncertain significance ★★ same type
- TYROBP p.Ser99Leu Uncertain significance ★★ ⚠ same type
- TYROBP p.Val38Met 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/tyrobp-p-ile46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown