DNMT3B p.His447=
c.1341C>T · rs552413219 · VCV2043571
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00891%, eas)
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. | ||
| REVEL | 0.224 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.65 | GERP -1.3, phastCons 0.01 |
| Overall | ||
| CADD | 5.277 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00891%
East Asian · 4/44,890 alleles
Filtering AF
0.00298%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0018%
Overall
0.000681%
11/1,614,212 alleles · very rare
exomes 10/1,461,894 · genomes 1/152,318 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00891% | 11,223 |
| Admixed American | 0.00167% | 60,030 |
| African / African-American | 0.00133% | 75,052 |
| South Asian | 0.0011% | 91,082 |
| European (non-Finnish) | 0.000339% | 295,008 |
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.His447=
- Coding
- c.1341C>T
- MANE Select
- NM_006892
- dbSNP
- rs552413219
- Type
- single nucleotide variant
- Location
- chr20:32796833 (GRCh38)
- Gene constraint
- LOEUF 0.396 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.18 · 47 PDB
- Residue 447
- the add domain; the 'interaction with the prc2/eed-ezh2 complex' region
Similar variants
- 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
- DNMT3B p.Val613Ala Pathogenic/Likely pathogenic ★★ same condition
- DNMT3B p.Val726Gly 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/dnmt3b-p-his447 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown