SETD1B p.Ala1049=
c.3147G>A · rs374996014 · VCV2643460
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0521%, 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 -14 | GERP -2.2 |
| Overall | ||
| CADD | 0.046 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0521%
European (non-Finnish) · 597/1,146,950 alleles
Filtering AF
0.0486%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0472%
Overall
0.0422%
655/1,551,442 alleles · ultra-rare
exomes 611/1,399,228 · genomes 44/152,214 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0521% | 1,921 |
| Remaining individualsnot grpmax-eligible | 0.0499% | 2,003 |
| Admixed American | 0.0275% | 3,642 |
| African / African-American | 0.0123% | 8,117 |
| East Asian | 0.00733% | 13,641 |
| South Asian | 0.00238% | 42,035 |
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.Ala1049=
- Coding
- c.3147G>A
- MANE Select
- NM_001353345
- dbSNP
- rs374996014
- Type
- single nucleotide variant
- Location
- chr12:121817539 (GRCh38)
- Gene constraint
- LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 46.43 · 4 PDB
- Residue 1049
- 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-ala1049 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown