DONSON p.Lys457=
c.1371G>A · rs139451211 · VCV727169
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.498%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.473 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.8 | GERP 4, phastCons 1 |
| Overall | ||
| CADD | 11.88 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.498%
African / African-American · 374/75,044 alleles
Filtering AF
0.457%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.44%
Overall
0.0261%
422/1,614,058 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.498% | 201 |
| Admixed American | 0.0416% | 2,401 |
| Remaining individualsnot grpmax-eligible | 0.0192% | 5,208 |
| Middle Eastern | 0.0165% | 6,062 |
| South Asian | 0.00329% | 30,362 |
| European (non-Finnish) | 0.000593% | 168,561 |
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.Lys457=
- Coding
- c.1371G>A
- MANE Select
- NM_017613
- dbSNP
- rs139451211
- Type
- single nucleotide variant
- Location
- chr21:33579542 (GRCh38)
- Gene constraint
- LOEUF 0.918 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.94
- Residue 457
- a UniProt-annotated variant site (in missla)
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-lys457 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown