SETD1A p.Pro613=
c.1839T>G · rs143686815 · VCV777020
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 16.3%, 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 -5.2 | GERP -3.5 |
| Overall | ||
| CADD | 0.496 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
16.3%
East Asian · 1,837/11,302 alleles
Filtering AF
15.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 15.4%
Overall
1.98%
15,415/777,342 alleles · common
exomes 14,296/755,598 · genomes 1,119/21,744 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 16.3% | 6 |
| Finnishnot grpmax-eligible | 7.62% | 13 |
| Amishnot grpmax-eligible | 3.47% | 29 |
| Remaining individualsnot grpmax-eligible | 1.99% | 50 |
| European (non-Finnish) | 1.71% | 58 |
| Ashkenazi Jewishnot grpmax-eligible | 1.14% | 88 |
| African / African-American | 1.02% | 98 |
| Admixed American | 0.574% | 174 |
| Middle Eastern | 0.461% | 217 |
| South Asian | 0.344% | 291 |
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
- SETD1A
- Protein
- p.Pro613=
- Coding
- c.1839T>G
- MANE Select
- NM_014712
- dbSNP
- rs143686815
- Type
- single nucleotide variant
- Location
- chr16:30965720 (GRCh38)
- Gene constraint
- LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.20 · 4 PDB
- Residue 613
- a UniProt-annotated variant site (in nedsid); the 'disordered' region
Similar variants
- SETD1A c.518-2A>G Pathogenic ★★ same type
- SETD1A p.Arg1571Ter Pathogenic/Likely pathogenic ★★ same type
- SETD1A p.Arg176Ter Pathogenic/Likely pathogenic ★★ same type
- SETD1A p.Arg668Ter Pathogenic ★★ same type
- SETD1A p.Arg913Cys Likely pathogenic ★★ ⚠ same type
- SETD1A p.Arg990Ter Pathogenic/Likely pathogenic ★★ same type
- SETD1A p.Tyr646Ter Pathogenic ★★ same type
- SETD1A c.4692+3G>A 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/setd1a-p-pro613 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown