DONSON p.Tyr270=
c.810T>C · rs374570179 · VCV2201724
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0034%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.058 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.5 | GERP 3.5, phastCons 1 |
| Overall | ||
| CADD | 7.157 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0034%
European (non-Finnish) · 40/1,178,154 alleles
Filtering AF
0.00256%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00225%
Overall
0.00273%
44/1,610,738 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0034% | 29,454 |
| Admixed American | 0.00335% | 29,826 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,290 |
| African / African-American | 0.00134% | 74,882 |
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.Tyr270=
- Coding
- c.810T>C
- MANE Select
- NM_017613
- dbSNP
- rs374570179
- Type
- single nucleotide variant
- Location
- chr21:33583642 (GRCh38)
- Gene constraint
- LOEUF 0.918 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.94
Similar variants
- DONSON p.Tyr270Cys Conflicting classifications of pathogenicity ★ ⚠ 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-tyr270 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown