TYROBP p.Ser103=
c.309C>T · VCV4822276
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00668%, 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 |
|---|---|---|
| Pangolin | Δ0.22 | loss · gain 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.35 | GERP -3.4, phastCons 0.001 |
| Overall | ||
| CADD | 6.449 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
East Asian · 3/44,888 alleles
Filtering AF
0.00177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.000682%
11/1,613,380 alleles · very rare
exomes 10/1,461,388 · genomes 1/151,992 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00668% | 14,963 |
| South Asian | 0.0033% | 30,306 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,230 |
| Finnishnot grpmax-eligible | 0.00156% | 63,958 |
| African / African-American | 0.00134% | 74,822 |
| European (non-Finnish) | 8.48e-05% | 1,179,842 |
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.Ser103=
- Coding
- c.309C>T
- MANE Select
- NM_003332
- Type
- single nucleotide variant
- Location
- chr19:35904602 (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 103
- the itam domain; the 'disordered' region
Similar variants
- 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
- TYROBP p.Val42Met 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-ser103 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown