DONSON p.Lys489Thr
c.1466A>C · rs146664036 · VCV431445
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1484 | likely benign |
|---|---|---|
| REVEL | 0.108 | moderately benign-leaning |
| SaProt | LLR -4.30 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>A here scores Δ0.50 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -7.6 | GERP -12 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 10 kb · p 0.95 · regional, not allelic |
| Overall | ||
| CADD | 0.036 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.693% | 144 |
| Middle Easterngrpmax | 0.379% | 264 |
| Remaining individualsnot grpmax-eligible | 0.17% | 590 |
| Admixed American | 0.125% | 800 |
| European (non-Finnish) | 0.085% | 1,176 |
| South Asian | 0.0582% | 1,719 |
| African / African-American | 0.0213% | 4,691 |
| Finnishnot grpmax-eligible | 0.0187% | 5,336 |
| East Asian | 0.0111% | 8,976 |
Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Lys489Thr
- Coding
- c.1466A>C
- MANE Select
- NM_017613
- dbSNP
- rs146664036
- Type
- single nucleotide variant
- Location
- chr21:33579447 (GRCh38)
- Gene constraint
- LOEUF 0.918 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.94
- Residue 489
- a UniProt-annotated variant site (in missla); a UniProt-annotated variant site (in missla; uncertain significance; reduced protein level; no effect on nuclear localization; does not complement loss of endogenous donson when tested for the rescue of the spontaneous fork stalling observed after donson depletion)
Disease context
Also linked: microcephalymicrocephaly-micromelia syndromemicrocephaly, short stature, and limb abnormalities
Similar variants
- DONSON p.Lys489Arg Benign/Likely benign ★★ same residue
- DONSON c.1047-9A>G Pathogenic ★★ same condition
- DONSON c.1563+1G>T Pathogenic ★★ same condition
- DONSON p.Arg293Ter Pathogenic ★★ same condition
- DONSON p.Gln428Ter Pathogenic/Likely pathogenic ★★ same condition
- DONSON p.Phe165Ser Pathogenic/Likely pathogenic ★★ same condition
- DONSON p.Ile307Val Uncertain significance ★★ ⚠ same condition
- DONSON p.Gln101Ter Likely pathogenic ★ same condition
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-lys489thr (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown