SETD1B p.Tyr136=
c.408C>T · rs374648258 · VCV3037185
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00959%, 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 2.2 | GERP -0.47, phastCons 1 |
| Overall | ||
| CADD | 11.14 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00959%
European (non-Finnish) · 110/1,146,998 alleles
Filtering AF
0.00813%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00757%
Overall
0.00735%
114/1,551,554 alleles · very rare
exomes 111/1,399,416 · genomes 3/152,138 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00959% | 10,427 |
| Remaining individualsnot grpmax-eligible | 0.00333% | 30,048 |
| African / African-American | 0.00274% | 36,512 |
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.Tyr136=
- Coding
- c.408C>T
- MANE Select
- NM_001353345
- dbSNP
- rs374648258
- Type
- single nucleotide variant
- Location
- chr12:121805969 (GRCh38)
- Gene constraint
- LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 46.43 · 4 PDB
- Residue 136
- the rrm domain; a β-strand
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-tyr136 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown