SETD1B p.Ile1847=
c.5541C>T · VCV3353051
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0086%, nfe)
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 -10 | GERP -3.9 |
| Overall | ||
| CADD | 2.31 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0086%
European (non-Finnish) · 99/1,150,778 alleles
Filtering AF
0.0072%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00668%
Overall
0.0068%
106/1,559,086 alleles · very rare
exomes 97/1,406,870 · genomes 9/152,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0086% | 11,624 |
| Remaining individualsnot grpmax-eligible | 0.00496% | 20,149 |
| African / African-American | 0.00272% | 36,698 |
| East Asian | 0.0024% | 41,656 |
| Admixed American | 0.00192% | 52,010 |
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
- SETD1B
- Protein
- p.Ile1847=
- Coding
- c.5541C>T
- MANE Select
- NM_001353345
- Type
- single nucleotide variant
- Location
- chr12:121827806 (GRCh38)
- Gene constraint
- LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 46.43 · 4 PDB
- Residue 1847
- the set domain; a UniProt-annotated variant site (in iddseld)
Similar variants
- SETD1B p.Arg1329Ter Pathogenic ★★ same type
- SETD1B p.Arg1703Ter Pathogenic/Likely pathogenic ★★ same type
- SETD1B p.Arg1748Cys Pathogenic/Likely pathogenic ★★ same type
- SETD1B p.Arg1792Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- SETD1B p.Arg1825Trp Likely pathogenic ★★ same type
- SETD1B p.Arg1902Cys Pathogenic/Likely pathogenic ★★ same type
- SETD1B p.Gln780Ter Pathogenic/Likely pathogenic ★★ same type
- SETD1B p.Glu1948Lys Pathogenic/Likely pathogenic ★★ 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/setd1b-p-ile1847 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown