SETD1B p.Pro699del
c.2079ACC[3] · VCV4918951
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.109%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -2.7 |
| Overall | ||
| CADD | 4.127 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.109%
Middle Eastern · 3/2,762 alleles
Filtering AF
0.0482%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0415%
Overall
0.0219%
229/1,045,172 alleles · rare
exomes 218/919,822 · genomes 11/125,350 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.109% | 921 |
| Admixed American | 0.0684% | 1,463 |
| Remaining individualsnot grpmax-eligible | 0.0663% | 1,509 |
| European (non-Finnish) | 0.0212% | 4,707 |
| East Asian | 0.00954% | 10,485 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00603% | 16,580 |
| South Asian | 0.00447% | 22,367 |
| African / African-American | 0.00372% | 26,904 |
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.Pro699del
- Coding
- c.2079ACC[3]
- MANE Select
- NM_001353345
- Type
- Microsatellite
- Location
- chr12:121814292 (GRCh38)
- Gene constraint
- LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 46.43 · 4 PDB
- Residue 699
- the 'disordered' region
Similar variants
- SETD1B p.Pro699Leu Uncertain significance ★ ⚠ same residue
- SETD1B p.Glu1087_Val1088insGlu Likely benign ★★ same type
- SETD1B p.Ile1933fs Likely pathogenic ★ same type
- SETD1B p.128EVE[1] Uncertain significance ★ same type
- SETD1B p.Glu1087_Val1088insGluGlu Uncertain significance ★ same type
- SETD1B p.Pro1596_Pro1598del Uncertain significance ★ same type
- SETD1B p.Ser1053del Uncertain significance ★ same type
- SETD1B p.Arg1022del Likely benign ★ 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-pro699del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown