DNMT3A p.Gly83=
c.249C>T · rs1337746913 · VCV2832914
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
Conditions
1
Tatton-Brown-Rahman overgrowth 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 |
|---|---|---|
| Pangolin | Δ0.25 | gain · loss 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 2.9 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 13.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/90,768 alleles
Filtering AF
0.000247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000159%
Overall
0.000496%
8/1,612,052 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0011% | 90,768 |
| European (non-Finnish) | 0.000594% | 168,451 |
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.Gly83=
- Coding
- c.249C>T
- MANE Select
- NM_022552
- dbSNP
- rs1337746913
- Type
- single nucleotide variant
- Location
- chr2:25282640 (GRCh38)
- Gene constraint
- LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.97 · 47 PDB
- Residue 83
- the 'disordered' region
Similar variants
- DNMT3A p.Gly83Asp Uncertain significance ★ ⚠ same residue
- 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.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-gly83 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown