DNMT3A p.Tyr683fs
c.2048_2053delinsC · VCV3342229
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 17 of 23 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 4.9 | GERP 0.81, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- DNMT3A
- Protein
- p.Tyr683fs
- Coding
- c.2048_2053delinsC
- MANE Select
- NM_022552
- Type
- Indel
- Location
- chr2:25241591 (GRCh38)
- Gene constraint
- LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.97 · 47 PDB
- Residue 683
- a β-strand; the sam-dependent mtase c5-type domain
Similar variants
- DNMT3A p.Tyr683= Likely benign ★ same residue
- DNMT3A c.1015-3_1015-1delinsAA Pathogenic ★ same type
- DNMT3A p.Asp22fs Likely pathogenic ★ same type
- DNMT3A c.1937-18_1937-17delinsTC Uncertain significance ★ same type
- DNMT3A p.Met674_Val675delinsIle Uncertain significance ★ same type
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-tyr683fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown