SETD5 p.His505=
c.1515T>C · rs117265865 · VCV773669
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.76%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.42 | GERP -4, phastCons 0.19 |
| Overall | ||
| CADD | 6.884 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.76%
East Asian · 2,136/44,838 alleles
Filtering AF
4.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.53%
Overall
0.148%
2,392/1,612,128 alleles · low-frequency
exomes 2,137/1,459,854 · genomes 255/152,274 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 4.76% | 21 |
| Remaining individualsnot grpmax-eligible | 0.21% | 476 |
| South Asian | 0.0738% | 1,356 |
| Admixed American | 0.0284% | 3,515 |
| Middle Eastern | 0.0165% | 6,044 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00339% | 29,532 |
| European (non-Finnish) | 0.00314% | 31,865 |
| African / African-American | 0.00267% | 37,471 |
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.His505=
- Coding
- c.1515T>C
- MANE Select
- NM_001080517
- dbSNP
- rs117265865
- Type
- single nucleotide variant
- Location
- chr3:9445731 (GRCh38)
- Gene constraint
- LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 47.10
- Residue 505
- the 'disordered' region; a UniProt-annotated variant site (in mrd23)
Similar variants
- SETD5 p.His505Tyr Uncertain significance ★★ ⚠ same residue
- SETD5 p.His505Pro 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
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-his505 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown