DNMT3B p.Lys685=
c.2055G>A · rs144497819 · VCV747122
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.677%, sas)
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 0.91 | GERP -2.4, phastCons 1 |
| Overall | ||
| CADD | 8.376 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.677%
South Asian · 617/91,082 alleles
Filtering AF
0.633%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.616%
Overall
0.0445%
718/1,614,172 alleles · rare
exomes 659/1,461,888 · genomes 59/152,284 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.677% | 148 |
| Remaining individualsnot grpmax-eligible | 0.0704% | 1,421 |
| African / African-American | 0.0173% | 5,772 |
| Middle Eastern | 0.0165% | 6,060 |
| European (non-Finnish) | 0.00339% | 29,501 |
| Admixed American | 0.00333% | 30,006 |
| East Asian | 0.00223% | 44,882 |
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.Lys685=
- Coding
- c.2055G>A
- MANE Select
- NM_006892
- dbSNP
- rs144497819
- Type
- single nucleotide variant
- Location
- chr20:32801336 (GRCh38)
- Gene constraint
- LOEUF 0.396 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.18 · 47 PDB
- Residue 685
- 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-lys685 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown