DNMT3A p.Glu285=
c.855G>A · rs1573342453 · VCV639320
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Tatton-Brown-Rahman overgrowth syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.42 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.38 | loss · gain 0.17 · SpliceAI calls gain · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 23.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- DNMT3A
- Protein
- p.Glu285=
- Coding
- c.855G>A
- MANE Select
- NM_022552
- dbSNP
- rs1573342453
- Type
- single nucleotide variant
- Location
- chr2:25248037 (GRCh38)
- Gene constraint
- LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.97 · 47 PDB
- Residue 285
- the 'interaction with dnmt1 and dnmt3b' region; the 'disordered' region
Similar variants
- DNMT3A p.Glu285Ter Pathogenic ★ same residue
- DNMT3A c.1667+1G>A Likely pathogenic ★★ same condition
- DNMT3A c.1937-2A>G Pathogenic ★★ same condition
- DNMT3A c.2478+1G>A Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A c.2479-1G>A Likely pathogenic ★★ same condition
- DNMT3A p.Arg143Ter Pathogenic ★★ same condition
- DNMT3A p.Arg320Ter Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A p.Arg598Ter Pathogenic/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/dnmt3a-p-glu285 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown