DNMT3A p.Arg556=
c.1668G>A · VCV4013945
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.51e-05%, nfe)
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 6 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 19.72 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.51e-05%
European (non-Finnish) · 1/1,174,564 alleles
Overall
6.9e-05%
1/1,449,992 alleles · very rare
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.Arg556=
- Coding
- c.1668G>A
- MANE Select
- NM_022552
- Type
- single nucleotide variant
- Location
- chr2:25244338 (GRCh38)
- Gene constraint
- LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.97 · 47 PDB
- Residue 556
- the 'interaction with the prc2/eed-ezh2 complex' region; the add domain
Similar variants
- DNMT3A p.Arg556Ser 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-arg556 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown