DNMT3A p.Gln80=
c.240G>A · rs528145106 · VCV864277
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00068%, nfe)
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 |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.3 | GERP 0.16, phastCons 1 |
| Overall | ||
| CADD | 7.994 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00068%
European (non-Finnish) · 8/1,176,102 alleles
Filtering AF
0.000293%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000212%
Overall
0.000498%
8/1,605,724 alleles · very rare
exomes 6/1,453,390 · genomes 2/152,334 · joint denominator
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.Gln80=
- Coding
- c.240G>A
- MANE Select
- NM_022552
- dbSNP
- rs528145106
- Type
- single nucleotide variant
- Location
- chr2:25282649 (GRCh38)
- Gene constraint
- LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.97 · 47 PDB
- Residue 80
- the 'disordered' region
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.Arg320Ter Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A p.Arg598Ter Pathogenic/Likely pathogenic ★★ same condition
- DNMT3A p.Arg688His 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-gln80 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown