TYROBP p.Ser31=
c.93C>T · VCV4528226
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00534%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.30 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.23 | loss · gain 0.03 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.92 | GERP -3.7 |
| Overall | ||
| CADD | 6.544 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00534%
African / African-American · 4/74,890 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00112%
18/1,613,984 alleles · very rare
exomes 17/1,461,860 · genomes 1/152,124 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00534% | 18,722 |
| Admixed American | 0.00167% | 59,996 |
| European (non-Finnish) | 0.0011% | 90,771 |
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.Ser31=
- Coding
- c.93C>T
- MANE Select
- NM_003332
- Type
- single nucleotide variant
- Location
- chr19:35907731 (GRCh38)
- Gene constraint
- LOEUF 1.274 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 64.10 · 5 PDB
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-ser31 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown