DNMT3A p.Asp530=
c.1590C>T · rs769420114 · VCV3032702
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00329%, sas)
Conditions
1
Inborn genetic diseases
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 -7 | GERP -3.7 |
| Overall | ||
| CADD | 4.274 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00329%
South Asian · 3/91,088 alleles
Filtering AF
0.000875%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000443%
Overall
0.000821%
12/1,461,866 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00329% | 30,363 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,512 |
| European (non-Finnish) | 0.000678% | 147,503 |
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.Asp530=
- Coding
- c.1590C>T
- MANE Select
- NM_022552
- dbSNP
- rs769420114
- Type
- single nucleotide variant
- Location
- chr2:25244617 (GRCh38)
- Gene constraint
- LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.97 · 47 PDB
- Residue 530
- the 'interaction with the prc2/eed-ezh2 complex' region; the add domain
Similar variants
- DNMT3A p.Asp530Asn Uncertain significance ★ ⚠ same residue
- DNMT3A p.Arg301Trp Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A p.Arg320Ter Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A p.Arg688His Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A p.Met548Thr Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A p.Pro904Leu Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A c.448+48C>G Uncertain significance ★★ same condition
- DNMT3A p.Arg544His 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-asp530 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown