DONSON p.Arg88=
c.264G>A · rs771966526 · VCV1631747
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0504%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.052 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.077 | GERP 2.7 |
| Overall | ||
| CADD | 8.085 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0504%
Middle Eastern · 2/3,966 alleles
Filtering AF
0.0405%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0392%
Overall
0.0378%
488/1,292,022 alleles · ultra-rare
exomes 438/1,139,910 · genomes 50/152,112 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0504% | 1,983 |
| European (non-Finnish) | 0.0439% | 2,277 |
| Remaining individualsnot grpmax-eligible | 0.0333% | 3,004 |
| Admixed American | 0.0319% | 3,135 |
| African / African-American | 0.0138% | 7,222 |
| Finnishnot grpmax-eligible | 0.00856% | 11,687 |
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.Arg88=
- Coding
- c.264G>A
- MANE Select
- NM_017613
- dbSNP
- rs771966526
- Type
- single nucleotide variant
- Location
- chr21:33588378 (GRCh38)
- Gene constraint
- LOEUF 0.918 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.94
- Residue 88
- the 'disordered' region
Similar variants
- 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
- DONSON p.Ala429Glu 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-arg88 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown