DONSON p.Thr161=
c.483G>A · rs761731134 · VCV2964139
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00534%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.339 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.036 | GERP -3.8, phastCons 0.031 |
| Overall | ||
| CADD | 8.474 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00534%
African / African-American · 4/74,902 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.000744%
12/1,613,986 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00534% | 18,726 |
| South Asian | 0.0022% | 45,543 |
| European (non-Finnish) | 0.000508% | 196,670 |
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.Thr161=
- Coding
- c.483G>A
- MANE Select
- NM_017613
- dbSNP
- rs761731134
- Type
- single nucleotide variant
- Location
- chr21:33586101 (GRCh38)
- Gene constraint
- LOEUF 0.918 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.94
Similar variants
- DONSON p.Thr161Met Uncertain significance ★★ ⚠ same residue
- DONSON p.Thr161Pro Uncertain significance ★ ⚠ same residue
- DONSON p.Thr161Ser 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
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-thr161 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown