SETD2 p.Pro2379=
c.7137G>A · rs768154988 · VCV1109959
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0147%, 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 0.44 | GERP -2.4, phastCons 1 |
| Overall | ||
| CADD | 11.47 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0147%
African / African-American · 11/74,618 alleles
Filtering AF
0.00818%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00636%
Overall
0.00143%
23/1,610,676 alleles · ultra-rare
exomes 14/1,458,802 · genomes 9/151,874 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0147% | 6,783 |
| South Asian | 0.00441% | 22,664 |
| Admixed American | 0.00169% | 59,194 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,316 |
| European (non-Finnish) | 0.000509% | 196,472 |
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.Pro2379=
- Coding
- c.7137G>A
- MANE Select
- NM_014159
- dbSNP
- rs768154988
- Type
- single nucleotide variant
- Location
- chr3:47042662 (GRCh38)
- Gene constraint
- LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.81 · 43 PDB
- Residue 2379
- a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation); a UniProt-annotated variant site (in all; uncertain significance; somatic mutation); an α-helix
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-pro2379 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown