TYROBP p.Thr37=
c.111G>A · rs200694727 · VCV737347
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.109%, eas)
Conditions
1
polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1
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 -20 | GERP -3.7 |
| Overall | ||
| CADD | 0.056 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.109%
East Asian · 49/44,886 alleles
Filtering AF
0.0848%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0761%
Overall
0.00372%
60/1,614,088 alleles · rare
exomes 51/1,461,824 · genomes 9/152,264 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.109% | 916 |
| Admixed American | 0.005% | 20,001 |
| South Asian | 0.00329% | 30,363 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,253 |
| African / African-American | 0.00133% | 75,026 |
| European (non-Finnish) | 0.000169% | 590,016 |
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.Thr37=
- Coding
- c.111G>A
- MANE Select
- NM_003332
- dbSNP
- rs200694727
- Type
- single nucleotide variant
- Location
- chr19:35907564 (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 37
- an α-helix
Similar variants
- TYROBP p.Val38Met Uncertain significance ★★ ⚠ same condition
- TYROBP p.Val47Ala Uncertain significance ★★ ⚠ same condition
- TYROBP c.94+10G>C Benign ★★ same condition
- TYROBP c.*140T>C Benign/Likely benign ★★ same condition
- TYROBP c.*25A>C Benign ★★ same condition
- TYROBP c.*83C>T Benign/Likely benign ★★ same condition
- TYROBP p.Arg23His Benign/Likely benign ★★ same condition
- TYROBP p.Val55Leu Benign ★★ same condition
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-thr37 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown