DNMT3A p.Ile780=
c.2340T>C · VCV3353382
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
DNMT3A-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.3 | GERP -0.48, phastCons 1 |
| Overall | ||
| CADD | 7.8 | 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.Ile780=
- Coding
- c.2340T>C
- MANE Select
- NM_022552
- Type
- single nucleotide variant
- Location
- chr2:25239198 (GRCh38)
- Gene constraint
- LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.97 · 47 PDB
- Residue 780
- a β-strand; the sam-dependent mtase c5-type domain
Disease context
DNMT3A-related disorder
Similar variants
- DNMT3A p.Ile780fs Likely pathogenic ★ same residue
- DNMT3A p.Ile780Thr Uncertain significance ★ ⚠ same residue
- DNMT3A c.1667+1G>A Likely pathogenic ★★ same condition
- DNMT3A p.Arg771Ter Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A p.Leu508Pro Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A p.Trp601Ter Pathogenic ★★ same condition
- DNMT3A p.Val636Met Likely pathogenic ★★ same condition
- DNMT3A p.Arg379Cys 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-ile780 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown