DNMT3B p.Arg127=
c.381G>A · rs2515512226 · VCV2848707
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
Conditions
1
immunodeficiency-centromeric instability-facial anomalies syndrome
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 0.031 | GERP -2.9, phastCons 0.045 |
| Overall | ||
| CADD | 8.118 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,046 alleles
Overall
6.84e-05%
1/1,461,548 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
- DNMT3B
- Protein
- p.Arg127=
- Coding
- c.381G>A
- MANE Select
- NM_006892
- dbSNP
- rs2515512226
- Type
- single nucleotide variant
- Location
- chr20:32786576 (GRCh38)
- Gene constraint
- LOEUF 0.396 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.18 · 47 PDB
- Residue 127
- the 'interaction with dnmt1 and dnmt3a' region; the 'disordered' region
Similar variants
- DNMT3B p.Arg127Gln Uncertain significance ★★ ⚠ same residue
- DNMT3B p.Arg127Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
- DNMT3B c.2421-11G>A Pathogenic/Likely pathogenic ★★ same condition
- DNMT3B p.Ala603Thr Pathogenic/Likely pathogenic ★★ same condition
- DNMT3B p.Arg826Cys Pathogenic/Likely pathogenic ★★ same condition
- DNMT3B p.Arg840Gln Likely pathogenic ★★ same condition
- DNMT3B p.Asp653Asn Pathogenic/Likely pathogenic ★★ same condition
- DNMT3B p.His814Arg 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/dnmt3b-p-arg127 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown