DNMT3A p.Asp22=
c.66C>T · rs2034256009 · VCV3054293
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00392%, amr)
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 4.8 | GERP 1.5, phastCons 1 |
| Overall | ||
| CADD | 10.78 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00392%
Admixed American · 2/50,990 alleles
Filtering AF
0.00065%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000243%
Overall
0.000194%
3/1,549,510 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00392% | 25,495 |
| African / African-American | 0.00137% | 73,040 |
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.Asp22=
- Coding
- c.66C>T
- MANE Select
- NM_022552
- dbSNP
- rs2034256009
- Type
- single nucleotide variant
- Location
- chr2:25313919 (GRCh38)
- Gene constraint
- LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.97 · 47 PDB
- Residue 22
- the 'disordered' region
Disease context
DNMT3A-related disorder
Similar variants
- DNMT3A p.Asp22Val Uncertain significance ⚠ same residue
- DNMT3A p.Asp22fs Likely pathogenic ★ same residue
- DNMT3A p.Asp22Asn 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
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-asp22 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown