SETD2 p.Pro186=
c.558G>A · rs183095591 · VCV542237
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.137%, 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 | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.5 | GERP -1.4, phastCons 1 |
| Overall | ||
| CADD | 9.043 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.137%
East Asian · 56/40,920 alleles
Filtering AF
0.108%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0979%
Overall
0.0119%
185/1,551,756 alleles · rare
exomes 159/1,399,590 · genomes 26/152,166 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.137% | 731 |
| Middle Eastern | 0.0334% | 2,995 |
| Remaining individualsnot grpmax-eligible | 0.015% | 6,686 |
| African / African-American | 0.00957% | 10,445 |
| European (non-Finnish) | 0.00942% | 10,620 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00349% | 28,654 |
| Finnishnot grpmax-eligible | 0.00167% | 59,946 |
| South Asian | 0.00119% | 84,058 |
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.Pro186=
- Coding
- c.558G>A
- MANE Select
- NM_014159
- dbSNP
- rs183095591
- Type
- single nucleotide variant
- Location
- chr3:47124078 (GRCh38)
- Gene constraint
- LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.81 · 43 PDB
- Residue 186
- a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation); the 'disordered' region
Similar variants
- SETD2 p.Pro186Leu Benign/Likely benign ★★ same residue
- SETD2 p.Pro186Ala Uncertain significance ★ ⚠ same residue
- SETD2 p.Pro186Arg Likely benign ★ same residue
- 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
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-pro186 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown