DNMT3A p.Asp81=
c.243C>T · VCV3351472
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000765%, nfe)
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 6.5 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 11.49 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000765%
European (non-Finnish) · 9/1,176,694 alleles
Filtering AF
0.00036%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000261%
Overall
0.000619%
9/1,454,650 alleles · very 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.Asp81=
- Coding
- c.243C>T
- MANE Select
- NM_022552
- Type
- single nucleotide variant
- Location
- chr2:25282646 (GRCh38)
- Gene constraint
- LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.97 · 47 PDB
- Residue 81
- the 'disordered' region
Disease context
DNMT3A-related disorder
Similar variants
- 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
- DNMT3A p.Arg55His Uncertain significance ★★ ⚠ same condition
- DNMT3A p.Ile490Thr 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-asp81 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown