DNMT3A p.Pro896=
c.2688A>G · rs181757577 · VCV541937
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.39%, 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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.9 | GERP -3.7 |
| Overall | ||
| CADD | 3.166 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.39%
Admixed American · 835/60,018 alleles
Filtering AF
1.31%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.28%
Overall
0.0547%
883/1,614,148 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 1.39% | 72 |
| Remaining individualsnot grpmax-eligible | 0.048% | 2,083 |
| African / African-American | 0.0107% | 9,382 |
| Finnishnot grpmax-eligible | 0.00156% | 64,042 |
| European (non-Finnish) | 0.000763% | 131,112 |
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.Pro896=
- Coding
- c.2688A>G
- MANE Select
- NM_022552
- dbSNP
- rs181757577
- Type
- single nucleotide variant
- Location
- chr2:25234330 (GRCh38)
- Gene constraint
- LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.97 · 47 PDB
- Residue 896
- an α-helix; the sam-dependent mtase c5-type domain
Similar variants
- 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
- DNMT3A p.Arg598Ter 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-pro896 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown