SETD1B p.Lys447=
c.1341G>A · rs758331807 · VCV2643429
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.67%, 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 4.9 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 8.325 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.67%
Middle Eastern · 100/5,986 alleles
Filtering AF
1.41%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.31%
Overall
0.0428%
660/1,543,496 alleles · low-frequency
exomes 611/1,391,348 · genomes 49/152,148 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 1.67% | 60 |
| Admixed American | 0.122% | 822 |
| Remaining individualsnot grpmax-eligible | 0.0999% | 1,001 |
| European (non-Finnish) | 0.0351% | 2,845 |
| African / African-American | 0.0178% | 5,623 |
| South Asian | 0.0167% | 5,999 |
| Ashkenazi Jewishnot grpmax-eligible | 0.014% | 7,153 |
| Finnishnot grpmax-eligible | 0.00763% | 13,099 |
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.Lys447=
- Coding
- c.1341G>A
- MANE Select
- NM_001353345
- dbSNP
- rs758331807
- Type
- single nucleotide variant
- Location
- chr12:121810286 (GRCh38)
- Gene constraint
- LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 46.43 · 4 PDB
- Residue 447
- 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-lys447 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown