SETD2 p.His337=
c.1011T>C · rs769297861 · VCV1141353
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0131%, sas)
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 4.2 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 7.567 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0131%
South Asian · 11/83,908 alleles
Filtering AF
0.00731%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00562%
Overall
0.00071%
11/1,550,206 alleles · ultra-rare
exomes 11/1,397,910 · genomes 0/152,296 · joint denominator
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.His337=
- Coding
- c.1011T>C
- MANE Select
- NM_014159
- dbSNP
- rs769297861
- Type
- single nucleotide variant
- Location
- chr3:47123625 (GRCh38)
- Gene constraint
- LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.81 · 43 PDB
- Residue 337
- a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation); the 'disordered' 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-his337 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown