TYROBP p.Ser99=
c.297G>A · rs767843323 · VCV1519128
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00936%, 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 |
|---|---|---|
| Pangolin | Δ0.20 | loss · gain 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.67 | GERP -1.4, phastCons 0.041 |
| Overall | ||
| CADD | 11.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00936%
African / African-American · 7/74,816 alleles
Filtering AF
0.00438%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00309%
Overall
0.00136%
22/1,613,246 alleles · very rare
exomes 18/1,461,236 · genomes 4/152,010 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00936% | 10,688 |
| East Asian | 0.00891% | 11,220 |
| Admixed American | 0.00668% | 14,981 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,456 |
| South Asian | 0.0011% | 90,832 |
| European (non-Finnish) | 0.000424% | 235,954 |
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.Ser99=
- Coding
- c.297G>A
- MANE Select
- NM_003332
- dbSNP
- rs767843323
- Type
- single nucleotide variant
- Location
- chr19:35904614 (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 99
- the itam domain; the 'disordered' region
Similar variants
- TYROBP p.Ser99Leu Uncertain significance ★★ ⚠ same residue
- TYROBP p.Ser99Trp 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.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-ser99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown