SETD5 p.Asp228Ala
c.683A>C · VCV4740936
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9014 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9014 | likely pathogenic |
|---|---|---|
| REVEL | 0.781 | moderately pathogenic-leaning |
| SaProt | LLR -7.44 | tolerated |
| ⇒ AlphaMissense and REVEL call this damaging; SaProt does not. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 9.4 | GERP 0.69, phastCons 1 |
| Regional constraint | o/e 0.77 | unconstrained · MANE · 12 kb · p 2.7e-05 · regional, not allelic |
| Overall | ||
| CADD | 26.3 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- SETD5
- Protein
- p.Asp228Ala
- Coding
- c.683A>C
- MANE Select
- NM_001080517
- Type
- single nucleotide variant
- Location
- chr3:9440571 (GRCh38)
- Gene constraint
- LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 47.10
Similar variants
- SETD5 p.Asp228= Likely benign ★ 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-asp228ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown