SETD2 p.Leu1757=
c.5271C>T · rs144825663 · VCV475524
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Rare
rare (popmax 0.649%, nfe)
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 0.94 | GERP -2.5, phastCons 1 |
| Overall | ||
| CADD | 3.326 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.649%
European (non-Finnish) · 7,653/1,179,368 alleles
Filtering AF
0.637%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.632%
Overall
0.537%
8,655/1,611,750 alleles · rare
exomes 8,077/1,459,494 · genomes 578/152,256 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.649% | 154 |
| Remaining individualsnot grpmax-eligible | 0.529% | 189 |
| Ashkenazi Jewishnot grpmax-eligible | 0.487% | 205 |
| Finnishnot grpmax-eligible | 0.43% | 232 |
| Admixed American | 0.123% | 815 |
| South Asian | 0.108% | 923 |
| African / African-American | 0.105% | 948 |
| Middle Eastern | 0.0661% | 1,514 |
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.Leu1757=
- Coding
- c.5271C>T
- MANE Select
- NM_014159
- dbSNP
- rs144825663
- Type
- single nucleotide variant
- Location
- chr3:47088119 (GRCh38)
- Gene constraint
- LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.81 · 43 PDB
- Residue 1757
- a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation); a UniProt-annotated variant site (in all; uncertain significance; somatic mutation)
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-leu1757 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown