DONSON p.Leu484=
c.1452G>A · rs751836395 · VCV1955419
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00666%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.39 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.36 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.24 | GERP -1.5, phastCons 0.84 |
| Overall | ||
| CADD | 12.56 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00666%
Admixed American · 4/60,018 alleles
Filtering AF
0.00226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.000274%
4/1,461,860 alleles · very rare
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.Leu484=
- Coding
- c.1452G>A
- MANE Select
- NM_017613
- dbSNP
- rs751836395
- Type
- single nucleotide variant
- Location
- chr21:33579461 (GRCh38)
- Gene constraint
- LOEUF 0.918 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.94
- Residue 484
- 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-leu484 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown