SETD5 p.Ile576=
c.1728C>A · rs191615401 · VCV1408643
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0586%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.036 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.85 | GERP 0.007, phastCons 0.78 |
| Overall | ||
| CADD | 9.034 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0586%
African / African-American · 44/75,064 alleles
Filtering AF
0.0448%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.04%
Overall
0.00378%
61/1,614,036 alleles · ultra-rare
exomes 28/1,461,704 · genomes 33/152,332 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0586% | 1,706 |
| Admixed American | 0.015% | 6,669 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,243 |
| European (non-Finnish) | 0.000509% | 196,649 |
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.Ile576=
- Coding
- c.1728C>A
- MANE Select
- NM_001080517
- dbSNP
- rs191615401
- Type
- single nucleotide variant
- Location
- chr3:9447253 (GRCh38)
- Gene constraint
- LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 47.10
- Residue 576
- the 'disordered' region; a UniProt-annotated variant site (in mrd23)
Similar variants
- SETD5 p.Ile576fs Pathogenic ★ 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-ile576 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown