DNMT3A p.Lys744=
c.2232G>A · rs944224150 · VCV797913
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.8 | GERP 0.8, phastCons 1 |
| Overall | ||
| CADD | 10.33 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,018 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.00031%
5/1,613,976 alleles · very rare
exomes 5/1,461,674 · genomes 0/152,302 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,018 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,498 |
| European (non-Finnish) | 0.000254% | 393,301 |
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.Lys744=
- Coding
- c.2232G>A
- MANE Select
- NM_022552
- dbSNP
- rs944224150
- Type
- single nucleotide variant
- Location
- chr2:25240392 (GRCh38)
- Gene constraint
- LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.97 · 47 PDB
- Residue 744
- the sam-dependent mtase c5-type domain
Similar variants
- DNMT3A p.Lys744Thr Uncertain significance ★ ⚠ same residue
- DNMT3A c.1667+1G>A Likely pathogenic ★★ same condition
- DNMT3A c.1937-2A>G Pathogenic ★★ same condition
- DNMT3A c.2478+1G>A Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A c.2479-1G>A Likely pathogenic ★★ same condition
- DNMT3A p.Arg143Ter Pathogenic ★★ same condition
- DNMT3A p.Arg301Trp Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A p.Arg320Ter Pathogenic/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-lys744 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown