SETD2 p.Pro2361=
c.7083T>A · rs552916928 · VCV2727421
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0179%, eas)
Conditions
1
Luscan-Lumish 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 0.32 | GERP -3.5, phastCons 0.61 |
| Overall | ||
| CADD | 5.509 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0179%
East Asian · 8/44,622 alleles
Filtering AF
0.00888%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00644%
Overall
0.00056%
9/1,606,424 alleles · ultra-rare
exomes 8/1,454,136 · genomes 1/152,288 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0179% | 5,578 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 61,988 |
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
- SETD2
- Protein
- p.Pro2361=
- Coding
- c.7083T>A
- MANE Select
- NM_014159
- dbSNP
- rs552916928
- Type
- single nucleotide variant
- Location
- chr3:47046502 (GRCh38)
- Gene constraint
- LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.81 · 43 PDB
- Residue 2361
- a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation); a UniProt-annotated variant site (in all; uncertain significance; somatic mutation); the 'low charge region' region
Similar variants
- SETD2 p.Arg1598Ter Pathogenic/Likely pathogenic ★★ same condition
- SETD2 p.Arg1740Gln Pathogenic ★★ ⚠ same condition
- SETD2 p.Arg1740Trp Pathogenic/Likely pathogenic ★★ same condition
- SETD2 p.Ala1121Thr Uncertain significance ★★ ⚠ same condition
- SETD2 p.Ala679Val Uncertain significance ★★ ⚠ same condition
- SETD2 p.Arg1065Cys Uncertain significance ★★ same condition
- SETD2 p.Arg329Gln Uncertain significance ★★ ⚠ same condition
- SETD2 p.Arg368Gln Uncertain significance ★★ ⚠ 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/setd2-p-pro2361 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown