SETDB1 p.Leu241=
c.723A>G · rs142533394 · VCV724032
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.124%, 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 -1.3 | GERP -3.9 |
| Overall | ||
| CADD | 3.096 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.124%
European (non-Finnish) · 1,459/1,180,000 alleles
Filtering AF
0.118%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.116%
Overall
0.0988%
1,594/1,614,178 alleles · rare
exomes 1,504/1,461,840 · genomes 90/152,338 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.124% | 809 |
| Finnishnot grpmax-eligible | 0.101% | 985 |
| Remaining individualsnot grpmax-eligible | 0.064% | 1,563 |
| Admixed American | 0.0283% | 3,531 |
| African / African-American | 0.0173% | 5,774 |
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
- SETDB1
- Protein
- p.Leu241=
- Coding
- c.723A>G
- MANE Select
- NM_001366418
- dbSNP
- rs142533394
- Type
- single nucleotide variant
- Location
- chr1:150942901 (GRCh38)
- Gene constraint
- LOEUF 0.29 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 66.45 · 26 PDB
- Residue 241
- the tudor 1; degenerate domain; a β-strand
Similar variants
- SETDB1 c.261-3T>C Likely benign ★★ same type
- SETDB1 p.Ala1022Val Benign ★★ same type
- SETDB1 p.Pro469= Benign ★★ same type
- SETDB1 p.Pro530Leu Benign/Likely benign ★★ same type
- SETDB1 p.Pro978Leu Likely benign ★★ same type
- SETDB1 c.674-2A>G Uncertain significance ★ same type
- SETDB1 p.Arg1244Leu Uncertain significance ★ ⚠ same type
- SETDB1 p.Arg611Gln Uncertain significance ★ ⚠ 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/setdb1-p-leu241 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown