SETD2 p.Arg329=
c.985C>A · rs372869995 · VCV542236
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.295%, 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 | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 5.1 | GERP 1.5, phastCons 1 |
| Overall | ||
| CADD | 7.531 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.295%
African / African-American · 215/72,988 alleles
Filtering AF
0.262%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.25%
Overall
0.0149%
231/1,550,432 alleles · rare
exomes 108/1,398,174 · genomes 123/152,258 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.295% | 339 |
| Admixed American | 0.0178% | 5,628 |
| Middle Eastern | 0.0167% | 5,990 |
| Remaining individualsnot grpmax-eligible | 0.00666% | 15,012 |
| European (non-Finnish) | 0.000174% | 573,371 |
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.Arg329=
- Coding
- c.985C>A
- MANE Select
- NM_014159
- dbSNP
- rs372869995
- Type
- single nucleotide variant
- Location
- chr3:47123651 (GRCh38)
- Gene constraint
- LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.81 · 43 PDB
- Residue 329
- a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation); the 'disordered' region
Similar variants
- SETD2 p.Arg329Gln Uncertain significance ★★ ⚠ same residue
- SETD2 p.Arg329Trp Benign/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
- SETD2 p.Arg1065Cys 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-arg329 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown