SETD2 p.Asp1400=
c.4200T>C · rs1442033870 · VCV2653747
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 0.65 | GERP -2.9, phastCons 0.95 |
| Overall | ||
| CADD | 4.064 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,056 alleles
Filtering AF
0.000444%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000186%
3/1,613,022 alleles · ultra-rare
exomes 3/1,460,940 · genomes 0/152,082 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,056 |
| African / African-American | 0.00267% | 37,385 |
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.Asp1400=
- Coding
- c.4200T>C
- MANE Select
- NM_014159
- dbSNP
- rs1442033870
- Type
- single nucleotide variant
- Location
- chr3:47120436 (GRCh38)
- Gene constraint
- LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.81 · 43 PDB
- Residue 1400
- a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation); a UniProt-annotated variant site (in all; uncertain significance; somatic mutation); the 'disordered' region
Similar variants
- SETD2 p.Asp1400Val Uncertain significance ★ ⚠ same residue
- SETD2 p.Arg1598Ter Pathogenic/Likely pathogenic ★★ same type
- SETD2 p.Arg1740Gln Pathogenic ★★ ⚠ same type
- SETD2 p.Arg1740Trp Pathogenic/Likely pathogenic ★★ same type
- SETD2 p.Arg441Ter Likely pathogenic ★★ same type
- SETD2 p.Glu1718Lys Likely pathogenic ★★ ⚠ same type
- SETD2 c.4715+5G>A Uncertain significance ★★ same type
- SETD2 p.Ala1121Thr Uncertain significance ★★ ⚠ same type
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-asp1400 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown