DNMT3A p.Phe732del
c.2190CTT[1] · rs761103716 · VCV2629187
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00668%, eas)
Conditions
2
DNMT3A-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4.8 | GERP 0.78, phastCons 1 |
| Overall | ||
| CADD | 21.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
East Asian · 3/44,878 alleles
Filtering AF
0.00256%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00225%
Overall
0.00323%
52/1,611,398 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00668% | 14,959 |
| Finnishnot grpmax-eligible | 0.00626% | 15,971 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00341% | 29,368 |
| European (non-Finnish) | 0.00339% | 29,468 |
| Admixed American | 0.00168% | 59,656 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,370 |
| African / African-American | 0.00133% | 74,956 |
| South Asian | 0.0011% | 90,636 |
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.Phe732del
- Coding
- c.2190CTT[1]
- MANE Select
- NM_022552
- dbSNP
- rs761103716
- Type
- Microsatellite
- Location
- chr2:25240429 (GRCh38)
- Gene constraint
- LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.97 · 47 PDB
- Residue 732
- an α-helix; the sam-dependent mtase c5-type domain
Similar variants
- DNMT3A p.Ile780fs Likely pathogenic ★ same condition
- DNMT3A p.Phe752del Likely pathogenic ★ same condition
- DNMT3A c.1851+2_1851+3del Uncertain significance same condition
- DNMT3A c.2174-4_2174-3del Likely benign same condition
- 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
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-phe732del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown