DNMT3B p.Ser780=
c.2340G>A · rs151108199 · VCV2052111
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0506%, afr)
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 | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.77 | GERP -3.8, phastCons 1 |
| Overall | ||
| CADD | 7.992 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0506%
African / African-American · 38/75,030 alleles
Filtering AF
0.0379%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0334%
Overall
0.00366%
59/1,614,166 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0506% | 1,974 |
| Admixed American | 0.005% | 20,008 |
| Finnishnot grpmax-eligible | 0.00469% | 21,341 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
| South Asian | 0.0011% | 91,064 |
| European (non-Finnish) | 0.00102% | 98,337 |
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.Ser780=
- Coding
- c.2340G>A
- MANE Select
- NM_006892
- dbSNP
- rs151108199
- Type
- single nucleotide variant
- Location
- chr20:32806247 (GRCh38)
- Gene constraint
- LOEUF 0.396 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.18 · 47 PDB
- Residue 780
- an α-helix; the sam-dependent mtase c5-type domain
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-ser780 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown