DONSON p.Pro35=
c.105G>C · rs2015314 · VCV1297949
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 6.97%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.189 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.051 | GERP -2.7 |
| Overall | ||
| CADD | 8.869 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.97%
African / African-American · 4,483/64,294 alleles
Filtering AF
6.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.73%
Overall
0.918%
11,495/1,251,800 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 6.97% | 14 |
| Middle Eastern | 1.75% | 57 |
| Admixed American | 1.54% | 65 |
| Remaining individualsnot grpmax-eligible | 1.03% | 97 |
| Finnishnot grpmax-eligible | 0.716% | 140 |
| European (non-Finnish) | 0.578% | 173 |
| Amishnot grpmax-eligible | 0.329% | 304 |
| Ashkenazi Jewishnot grpmax-eligible | 0.301% | 332 |
| South Asian | 0.161% | 621 |
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
- DONSON
- Protein
- p.Pro35=
- Coding
- c.105G>C
- MANE Select
- NM_017613
- dbSNP
- rs2015314
- Type
- single nucleotide variant
- Location
- chr21:33588537 (GRCh38)
- Gene constraint
- LOEUF 0.918 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.94
- Residue 35
- the 'disordered' region
Similar variants
- DONSON p.Pro35Arg Uncertain significance ★ ⚠ same residue
- DONSON c.1047-9A>G Pathogenic ★★ same type
- DONSON c.1563+1G>T Pathogenic ★★ same type
- DONSON p.Arg293Ter Pathogenic ★★ same type
- DONSON p.Arg442Ter Pathogenic ★★ same type
- DONSON p.Gln428Ter Pathogenic/Likely pathogenic ★★ same type
- DONSON p.Phe165Ser Pathogenic/Likely pathogenic ★★ same type
- DONSON p.Ala32Gly 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/donson-p-pro35 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown