SETD5 p.Phe343=
c.1029C>T · rs995588965 · VCV2120948
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00224%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.04 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -0.26 | GERP -0.53, phastCons 0.2 |
| Overall | ||
| CADD | 13.31 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00224%
East Asian · 1/44,736 alleles
Filtering AF
0.000366%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000137%
Overall
0.000373%
6/1,609,996 alleles · very rare
exomes 4/1,460,694 · genomes 2/149,302 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00224% | 44,736 |
| South Asian | 0.0022% | 45,403 |
| European (non-Finnish) | 0.000255% | 392,841 |
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.Phe343=
- Coding
- c.1029C>T
- MANE Select
- NM_001080517
- dbSNP
- rs995588965
- Type
- single nucleotide variant
- Location
- chr3:9442197 (GRCh38)
- Gene constraint
- LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 47.10
- Residue 343
- the set domain
Similar variants
- SETD5 p.Phe343fs Pathogenic ★ 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-phe343 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown