DONSON p.Cys212=
c.636T>C · rs534844606 · VCV1662636
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.379%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.325 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.31 | GERP -3.4, phastCons 0.38 |
| Overall | ||
| CADD | 10.32 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.379%
South Asian · 338/89,152 alleles
Filtering AF
0.346%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.333%
Overall
0.0219%
351/1,600,514 alleles · rare
exomes 333/1,448,186 · genomes 18/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.379% | 264 |
| Remaining individualsnot grpmax-eligible | 0.0178% | 5,623 |
| Middle Eastern | 0.0166% | 6,022 |
| European (non-Finnish) | 8.53e-05% | 1,171,691 |
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.Cys212=
- Coding
- c.636T>C
- MANE Select
- NM_017613
- dbSNP
- rs534844606
- Type
- single nucleotide variant
- Location
- chr21:33584739 (GRCh38)
- Gene constraint
- LOEUF 0.918 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.94
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-cys212 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown