DNMT3A p.Arg882Ser
c.2644C>A · rs377577594 · VCV375884
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9997 | likely pathogenic · top 7% in DNMT3A |
|---|---|---|
| REVEL | 0.884 | moderately pathogenic-leaning |
| SaProt | LLR -14.71 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.7, phastCons 1 |
| Regional constraint | o/e 1.09 | unconstrained · MANE · 110 bp · p 0.5 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,600 |
| Admixed Americangrpmax | 0.00167% | 59,986 |
| European (non-Finnish) | 0.000763% | 131,082 |
Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.
Cancer therapy — CIViC
| Disease | Therapies | Level | Significance |
|---|---|---|---|
| Acute Myeloid Leukemia | Daunorubicin | B | Resistance |
| Acute Myeloid Leukemia | B | Negative | |
| Acute Myeloid Leukemia | B | Positive | |
| Acute Myeloid Leukemia | B | Better Outcome | |
| Acute Myeloid Leukemia | B | Positive | |
| Acute Myeloid Leukemia | B | Positive | |
| Acute Myeloid Leukemia | B | ||
| Acute Myeloid Leukemia | B | Better Outcome |
Variant & gene context
- Gene
- DNMT3A
- Protein
- p.Arg882Ser
- Coding
- c.2644C>A
- MANE Select
- NM_022552
- dbSNP
- rs377577594
- Type
- single nucleotide variant
- Location
- chr2:25234374 (GRCh38)
- Gene constraint
- LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.97 · 47 PDB
- Residue 882
- an α-helix; the sam-dependent mtase c5-type domain; a UniProt-annotated variant site (in tbrs and aml; somatic variant in aml); a UniProt-annotated variant site (in a patient with chronic myelomonocytic leukemia; somatic mutation)
Similar variants
- DNMT3A p.Arg882Cys Pathogenic/Likely pathogenic ★★ same residue
- DNMT3A p.Arg882His Pathogenic/Likely pathogenic ★★ same residue
- DNMT3A p.Arg882= Likely benign ★ 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
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-arg882ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown