SETD1A p.Ile1173=
c.3519C>T · VCV4929499
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0331%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.37 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.5 | GERP -4.4, phastCons 0.017 |
| Overall | ||
| CADD | 2.47 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0331%
Middle Eastern · 2/6,050 alleles
Filtering AF
0.00605%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00565%
Overall
0.0062%
100/1,613,380 alleles · ultra-rare
exomes 95/1,461,258 · genomes 5/152,122 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0331% | 3,025 |
| Admixed American | 0.0117% | 8,571 |
| European (non-Finnish) | 0.00738% | 13,559 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,576 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,243 |
| African / African-American | 0.00133% | 75,000 |
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.Ile1173=
- Coding
- c.3519C>T
- MANE Select
- NM_014712
- Type
- single nucleotide variant
- Location
- chr16:30979305 (GRCh38)
- Gene constraint
- LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.20 · 4 PDB
- Residue 1173
- the 'disordered' region; a UniProt-annotated variant site (in nedsid)
Similar variants
- SETD1A p.Ile1173Met Uncertain significance ★ ⚠ same residue
- SETD1A p.Ile1173Val Likely benign ★ same residue
- 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
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-ile1173 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown