SETD5 p.Ser41=
c.123C>A · rs548352059 · VCV713197
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0713%, 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 6 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 13.31 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0713%
East Asian · 32/44,864 alleles
Filtering AF
0.0519%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0452%
Overall
0.00223%
36/1,613,828 alleles · ultra-rare
exomes 28/1,461,634 · genomes 8/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0713% | 1,402 |
| Admixed American | 0.00333% | 30,004 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,480 |
| European (non-Finnish) | 8.48e-05% | 1,179,839 |
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.Ser41=
- Coding
- c.123C>A
- MANE Select
- NM_001080517
- dbSNP
- rs548352059
- Type
- single nucleotide variant
- Location
- chr3:9433896 (GRCh38)
- Gene constraint
- LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 47.10
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-ser41 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown