SETDB1 p.Pro469=
c.1407C>G · rs113296072 · VCV722333
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.429%, afr)
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 -3.4 | GERP -3.3 |
| Overall | ||
| CADD | 1.959 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.429%
African / African-American · 322/75,026 alleles
Filtering AF
0.391%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.375%
Overall
0.0223%
360/1,613,832 alleles · rare
exomes 172/1,461,558 · genomes 188/152,274 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.429% | 233 |
| Remaining individualsnot grpmax-eligible | 0.0368% | 2,717 |
| Admixed American | 0.0217% | 4,614 |
| East Asian | 0.00223% | 44,886 |
| European (non-Finnish) | 8.48e-05% | 1,179,888 |
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.Pro469=
- Coding
- c.1407C>G
- MANE Select
- NM_001366418
- dbSNP
- rs113296072
- Type
- single nucleotide variant
- Location
- chr1:150949261 (GRCh38)
- Gene constraint
- LOEUF 0.29 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 66.45 · 26 PDB
- Residue 469
- the 'disordered' region
Similar variants
- SETDB1 c.261-3T>C Likely benign ★★ same type
- SETDB1 p.Ala1022Val 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
- SETDB1 p.Asn245Asp 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-pro469 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown