SETD5 p.Leu286Pro
c.857T>C · VCV4961101
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9999 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
SETD5-related disorder
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9999 | likely pathogenic ✓ concordant with ClinVar · top 1% in SETD5 |
|---|---|---|
| REVEL | 0.963 | strongly pathogenic-leaning |
| SaProt | LLR -15.95 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 2, phastCons 1 |
| Regional constraint | o/e 0.45 | unconstrained · MANE · 1,051 bp · p 9.5e-06 · regional, not allelic |
| Overall | ||
| CADD | 27.8 | 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.Leu286Pro
- Coding
- c.857T>C
- MANE Select
- NM_001080517
- Type
- single nucleotide variant
- Location
- chr3:9441639 (GRCh38)
- Gene constraint
- LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 47.10
- Residue 286
- the set domain
Disease context
SETD5-related disorder
Similar variants
- SETD5 p.Arg1174Ter Pathogenic/Likely pathogenic ★★ same condition
- SETD5 p.Arg445Ter Pathogenic ★★ same condition
- SETD5 p.Arg768Ter Pathogenic ★★ same condition
- SETD5 p.Gln1058Ter Pathogenic/Likely pathogenic ★★ same condition
- SETD5 p.Gln272Ter Pathogenic/Likely pathogenic ★★ same condition
- SETD5 p.Tyr391Cys Likely pathogenic ★★ same condition
- SETD5 p.Ala259Thr Uncertain significance ★★ ⚠ same condition
- SETD5 p.Arg1190Ser Uncertain significance ★★ same condition
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-leu286pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown