SETD5 p.Pro428=
c.1284T>G · rs758949684 · VCV2055834
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00288%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.084 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.093 | GERP -2.2, phastCons 0.98 |
| Overall | ||
| CADD | 9.484 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00288%
European (non-Finnish) · 34/1,179,858 alleles
Filtering AF
0.00207%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00183%
Overall
0.00211%
34/1,613,654 alleles · very rare
exomes 29/1,461,674 · genomes 5/151,980 · joint denominator
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.Pro428=
- Coding
- c.1284T>G
- MANE Select
- NM_001080517
- dbSNP
- rs758949684
- Type
- single nucleotide variant
- Location
- chr3:9445144 (GRCh38)
- Gene constraint
- LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 47.10
- Residue 428
- the 'disordered' region; a UniProt-annotated variant site (in mrd23)
Similar variants
- 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
- SETD5 p.Arg1072Ter 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/setd5-p-pro428 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown