UNC13D p.Pro33=
c.99G>A · rs147886860 · VCV263249
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.63%, mid)
Conditions
2
autoinflammatory syndrome
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 -1.9 | |
| Overall | ||
| CADD | 9.919 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.63%
Middle Eastern · 159/6,050 alleles
Filtering AF
2.29%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.17%
Overall
0.0992%
1,599/1,612,112 alleles · low-frequency
exomes 1,459/1,459,818 · genomes 140/152,294 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 2.63% | 38 |
| Ashkenazi Jewishnot grpmax-eligible | 1.14% | 88 |
| Remaining individualsnot grpmax-eligible | 0.213% | 470 |
| Admixed American | 0.193% | 517 |
| South Asian | 0.149% | 670 |
| European (non-Finnish) | 0.0569% | 1,758 |
| African / African-American | 0.056% | 1,787 |
| East Asian | 0.00891% | 11,220 |
| Finnishnot grpmax-eligible | 0.00161% | 62,102 |
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
- UNC13D
- Protein
- p.Pro33=
- Coding
- c.99G>A
- MANE Select
- NM_199242
- dbSNP
- rs147886860
- Type
- single nucleotide variant
- Location
- chr17:75844239 (GRCh38)
- Gene constraint
- LOEUF 0.923 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.04 · 1 PDB
Similar variants
- UNC13D p.Pro33Gln Uncertain significance ★ ⚠ same residue
- UNC13D p.Pro33Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- UNC13D c.1055+1G>A Pathogenic/Likely pathogenic ★★ same condition
- UNC13D c.118-307G>A Pathogenic ★★ same condition
- UNC13D c.118-308C>T Pathogenic/Likely pathogenic ★★ same condition
- UNC13D c.1389+1G>A Pathogenic ★★ same condition
- UNC13D c.1596+1G>C Pathogenic ★★ same condition
- UNC13D c.1727+1G>A Pathogenic/Likely pathogenic ★★ 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/unc13d-p-pro33 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown