DNMT3A p.Glu725=
c.2175G>A · rs1295503544 · VCV500593
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.017%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.87 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.35 | gain · loss 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 24.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.017%
Middle Eastern · 1/5,886 alleles
Overall
0.000656%
1/152,350 alleles · ultra-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
- DNMT3A
- Protein
- p.Glu725=
- Coding
- c.2175G>A
- MANE Select
- NM_022552
- dbSNP
- rs1295503544
- Type
- single nucleotide variant
- Location
- chr2:25240449 (GRCh38)
- Gene constraint
- LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.97 · 47 PDB
- Residue 725
- a β-strand; the sam-dependent mtase c5-type domain
Similar variants
- DNMT3A p.Glu725Lys Uncertain significance ★ ⚠ same residue
- DNMT3A c.1667+1G>A Likely pathogenic ★★ same type
- DNMT3A c.1937-2A>G Pathogenic ★★ same type
- DNMT3A c.2478+1G>A Pathogenic/Likely pathogenic ★★ same type
- DNMT3A c.2479-1G>A Likely pathogenic ★★ same type
- DNMT3A p.Arg143Ter Pathogenic ★★ same type
- DNMT3A p.Arg301Trp Pathogenic/Likely pathogenic ★★ same type
- DNMT3A p.Arg320Ter Pathogenic/Likely pathogenic ★★ 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/dnmt3a-p-glu725 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown