SETD1B p.Ser1048=
c.3144C>T · VCV3770870
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00958%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.30 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.1 | GERP -2.2 |
| Overall | ||
| CADD | 0.913 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00958%
African / African-American · 7/73,064 alleles
Filtering AF
0.00562%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0052%
Overall
0.0058%
90/1,551,418 alleles · very rare
exomes 80/1,399,214 · genomes 10/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00958% | 10,438 |
| European (non-Finnish) | 0.00689% | 14,518 |
| Admixed American | 0.00392% | 25,489 |
| Remaining individualsnot grpmax-eligible | 0.00166% | 60,096 |
| South Asian | 0.00119% | 84,070 |
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.Ser1048=
- Coding
- c.3144C>T
- MANE Select
- NM_001353345
- Type
- single nucleotide variant
- Location
- chr12:121817536 (GRCh38)
- Gene constraint
- LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 46.43 · 4 PDB
- Residue 1048
- a UniProt-annotated variant site (in iddseld); the 'disordered' region
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-ser1048 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown