DNMT3A p.Arg309Pro
c.926G>C · VCV3841762
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9997 | likely pathogenic · top 7% in DNMT3A |
|---|---|---|
| REVEL | 0.664 | pathogenic-leaning |
| SaProt | LLR -15.22 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 1.49 | unconstrained · MANE · 65 bp · p 0.008 · regional, not allelic |
| Overall | ||
| CADD | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00133% | 74,914 |
| European (non-Finnish) | 8.47e-05% | 1,180,032 |
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
- DNMT3A
- Protein
- p.Arg309Pro
- Coding
- c.926G>C
- MANE Select
- NM_022552
- Type
- single nucleotide variant
- Location
- chr2:25247679 (GRCh38)
- Gene constraint
- LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.97 · 47 PDB
- Residue 309
- the pwwp domain; a β-strand; the 'interaction with dnmt1 and dnmt3b' region
Similar variants
- DNMT3A p.Arg309= Likely benign ★ same residue
- DNMT3A p.Arg309Cys Uncertain significance ★ ⚠ same residue
- DNMT3A p.Arg301Trp Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A p.Arg320Ter Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A p.Arg688His Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A p.Met548Thr Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A p.Pro904Leu Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A c.448+48C>G Uncertain significance ★★ 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/dnmt3a-p-arg309pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown