DNMT3A p.Ser349=
c.1047G>A · rs375328501 · VCV2042421
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
Conditions
2
Inborn genetic diseases
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 · C>A here scores Δ0.54 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.96 | GERP -2.8, phastCons 1 |
| Overall | ||
| CADD | 13.94 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,014 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000743%
12/1,614,076 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 20,005 |
| East Asian | 0.00223% | 44,882 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,510 |
| South Asian | 0.0011% | 91,072 |
| European (non-Finnish) | 0.000508% | 196,665 |
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.Ser349=
- Coding
- c.1047G>A
- MANE Select
- NM_022552
- dbSNP
- rs375328501
- Type
- single nucleotide variant
- Location
- chr2:25247126 (GRCh38)
- Gene constraint
- LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.97 · 47 PDB
- Residue 349
- the pwwp domain; the 'interaction with dnmt1 and dnmt3b' region; an α-helix
Similar variants
- DNMT3A c.1667+1G>A Likely pathogenic ★★ same condition
- DNMT3A c.1937-2A>G Pathogenic ★★ same condition
- DNMT3A c.2478+1G>A Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A c.2479-1G>A Likely pathogenic ★★ same condition
- DNMT3A p.Arg143Ter Pathogenic ★★ same condition
- DNMT3A p.Arg301Trp Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A p.Arg320Ter Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A p.Arg598Ter 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/dnmt3a-p-ser349 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown