SETD1B p.Leu577=
c.1731C>G · rs895952 · VCV1279948
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 98.9%, eas) — too common for a highly-penetrant pathogenic allele
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 2.5 | GERP -1.8, phastCons 1 |
| Overall | ||
| CADD | 0.948 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
98.9%
East Asian · 40,446/40,904 alleles
Filtering AF
98.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 97.7%
Overall
81.8%
1,268,044/1,549,898 alleles · common
exomes 1,148,965/1,397,766 · genomes 119,079/152,132 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 98.9% | 1 |
| South Asian | 89.6% | 1 |
| Admixed American | 88.3% | 1 |
| Amishnot grpmax-eligible | 87.2% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 86.8% | 1 |
| Middle Eastern | 85.1% | 1 |
| Remaining individualsnot grpmax-eligible | 82.8% | 1 |
| European (non-Finnish) | 81.4% | 1 |
| Finnishnot grpmax-eligible | 79.8% | 1 |
| African / African-American | 64.2% | 2 |
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.Leu577=
- Coding
- c.1731C>G
- MANE Select
- NM_001353345
- dbSNP
- rs895952
- Type
- single nucleotide variant
- Location
- chr12:121810676 (GRCh38)
- Gene constraint
- LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 46.43 · 4 PDB
- Residue 577
- 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-leu577 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown