DNMT3A c.448+48C>A
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00537%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.013 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| Splice region | donor +48 | near-intronic (+48 nt from the splice site) |
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.59 | GERP -0.017 |
| Non-coding constraint | Z 5.24 | 1 kb window · o/e 0.66 · regional · uncalibrated |
| Overall | ||
| CADD | 1.129 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00537%
African / African-American · 4/74,442 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.000252%
4/1,589,898 alleles · very rare
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
- Coding
- c.448+48C>A
- MANE Select
- NM_022552
- dbSNP
- rs778675092
- Type
- single nucleotide variant
- Location
- chr2:25282393 (GRCh38)
- Gene constraint
- LOEUF 1.998 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.97 · 47 PDB
Similar variants
- DNMT3A c.1667+1G>A Likely pathogenic ★★ same type
- DNMT3A c.1937-2A>G Pathogenic ★★ same type
- DNMT3A c.2478+1G>A Pathogenic/Likely pathogenic ★★ same type
- DNMT3A c.2479-1G>A Likely pathogenic ★★ same type
- DNMT3A p.Arg143Ter Pathogenic ★★ same type
- DNMT3A p.Arg301Trp Pathogenic/Likely pathogenic ★★ same type
- DNMT3A p.Arg320Ter Pathogenic/Likely pathogenic ★★ same type
- DNMT3A p.Arg598Ter Pathogenic/Likely pathogenic ★★ 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-c-448-plus-48c-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown