Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 8.66%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -14 | |
| Overall | ||
| CADD | 2.781 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.66%
African / African-American · 6,497/75,008 alleles
Filtering AF
8.49%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 8.41%
Overall
0.474%
7,646/1,613,862 alleles · common
exomes 3,939/1,461,618 · genomes 3,707/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 8.66% | 12 |
| Admixed American | 0.626% | 160 |
| Remaining individualsnot grpmax-eligible | 0.558% | 179 |
| Ashkenazi Jewishnot grpmax-eligible | 0.487% | 206 |
| Middle Eastern | 0.396% | 252 |
| European (non-Finnish) | 0.0203% | 4,937 |
| South Asian | 0.0165% | 6,070 |
| East Asian | 0.00668% | 14,961 |
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
- USP36
- Protein
- p.Pro346=
- Coding
- c.1038G>A
- MANE Select
- NM_001385174
- dbSNP
- rs7210763
- Type
- single nucleotide variant
- Location
- chr17:78814538 (GRCh38)
- Gene constraint
- LOEUF 0.645 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.88 · 2 PDB
- Residue 346
- the usp domain
Similar variants
- USP36 p.Pro346Leu Uncertain significance ★ ⚠ same residue
- USP36 p.Arg887Pro Benign ★★ same type
- USP36 p.Asn1096= Benign ★★ same type
- USP36 p.Asp270= Benign ★★ same type
- USP36 p.Gly444Ser Benign ★★ same type
- USP36 p.His200Asn Likely benign ★★ ⚠ same type
- USP36 p.Phe164= Benign/Likely benign ★★ same type
- USP36 p.Pro443= Benign ★★ 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/usp36-p-pro346 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown