SETD7 p.Pro22=
c.66G>A · rs35955363 · VCV786048
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.33%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.026 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -14 | GERP -3.7 |
| Overall | ||
| CADD | 3.525 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.33%
African / African-American · 3,244/74,990 alleles
Filtering AF
4.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.15%
Overall
0.233%
3,758/1,614,016 alleles · low-frequency
exomes 1,927/1,461,866 · genomes 1,831/152,150 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.33% | 23 |
| Remaining individualsnot grpmax-eligible | 0.368% | 272 |
| Admixed American | 0.303% | 330 |
| Middle Eastern | 0.165% | 606 |
| South Asian | 0.0626% | 1,598 |
| East Asian | 0.0178% | 5,610 |
| European (non-Finnish) | 0.00229% | 43,702 |
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
- SETD7
- Protein
- p.Pro22=
- Coding
- c.66G>A
- MANE Select
- NM_030648
- dbSNP
- rs35955363
- Type
- single nucleotide variant
- Location
- chr4:139547024 (GRCh38)
- Gene constraint
- LOEUF 0.605 · pLI 0.65 (gnomAD)
- Structure
- AlphaFold pLDDT 94.51 · 32 PDB
Similar variants
- SETD7 p.Arg115Cys Uncertain significance ★ ⚠ same type
- SETD7 p.Arg179Thr Uncertain significance ★ ⚠ same type
- SETD7 p.Asp101His Uncertain significance ★ ⚠ same type
- SETD7 p.Asp306Asn Uncertain significance ★ ⚠ same type
- SETD7 p.Cys288Ser Uncertain significance ★ ⚠ same type
- SETD7 p.Cys288Tyr Uncertain significance ★ ⚠ same type
- SETD7 p.Cys303Ser Uncertain significance ★ ⚠ same type
- SETD7 p.Gly102Arg Uncertain significance ★ ⚠ 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/setd7-p-pro22 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown