SETD5 p.Ala598=
c.1794A>G · rs376761696 · VCV436687
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.115%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.026 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 1.2 | GERP 0.63, phastCons 1 |
| Overall | ||
| CADD | 9.118 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.115%
European (non-Finnish) · 1,359/1,179,762 alleles
Filtering AF
0.11%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.108%
Overall
0.0902%
1,455/1,613,848 alleles · rare
exomes 1,371/1,461,506 · genomes 84/152,342 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.115% | 868 |
| Remaining individualsnot grpmax-eligible | 0.0704% | 1,420 |
| Admixed American | 0.0433% | 2,308 |
| African / African-American | 0.0173% | 5,774 |
| Middle Eastern | 0.0165% | 6,060 |
| South Asian | 0.011% | 9,108 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,586 |
| Finnishnot grpmax-eligible | 0.00156% | 64,012 |
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
- SETD5
- Protein
- p.Ala598=
- Coding
- c.1794A>G
- MANE Select
- NM_001080517
- dbSNP
- rs376761696
- Type
- single nucleotide variant
- Location
- chr3:9447697 (GRCh38)
- Gene constraint
- LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 47.10
- Residue 598
- the 'disordered' region; a UniProt-annotated variant site (in mrd23)
Similar variants
- SETD5 p.Ala598Thr Uncertain significance ★ ⚠ same residue
- SETD5 c.1441-1G>A Pathogenic ★★ same type
- SETD5 c.1525-1G>C Pathogenic/Likely pathogenic ★★ same type
- SETD5 c.2347-1G>A Pathogenic ★★ same type
- SETD5 c.2347-7A>G Pathogenic ★★ same type
- SETD5 c.3631+1G>A Pathogenic ★★ same type
- SETD5 c.960-5C>G Pathogenic/Likely pathogenic ★★ same type
- SETD5 p.Arg1001Ter 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/setd5-p-ala598 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown