SETD2 p.Pro2160=
c.6480G>A · VCV4808542
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0253%, afr)
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 -0.027 | GERP -3.5, phastCons 0.02 |
| Overall | ||
| CADD | 7.24 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0253%
African / African-American · 19/75,024 alleles
Filtering AF
0.0165%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0137%
Overall
0.00316%
51/1,614,148 alleles · ultra-rare
exomes 32/1,461,890 · genomes 19/152,258 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0253% | 3,949 |
| Admixed American | 0.0183% | 5,456 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,627 |
| East Asian | 0.00446% | 22,440 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
| South Asian | 0.0022% | 45,539 |
| Finnishnot grpmax-eligible | 0.00156% | 64,034 |
| European (non-Finnish) | 0.000932% | 107,275 |
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.Pro2160=
- Coding
- c.6480G>A
- MANE Select
- NM_014159
- Type
- single nucleotide variant
- Location
- chr3:47057304 (GRCh38)
- Gene constraint
- LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.81 · 43 PDB
- Residue 2160
- 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.Pro2160Leu Uncertain significance ★★ ⚠ 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
- SETD2 p.Arg1065Cys Uncertain significance ★★ same condition
- SETD2 p.Arg329Gln 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-pro2160 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown