MBD4 p.Ala293=
c.879T>C · rs770049431 · VCV2654124
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000339%, nfe)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>T here scores Δ0.58 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.2 | GERP -1.2, phastCons 0.53 |
| Overall | ||
| CADD | 4.384 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000339%
European (non-Finnish) · 4/1,180,016 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.000248%
4/1,613,988 alleles · very rare
exomes 3/1,461,824 · genomes 1/152,164 · 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
- MBD4
- Protein
- p.Ala293=
- Coding
- c.879T>C
- MANE Select
- NM_001276270
- dbSNP
- rs770049431
- Type
- single nucleotide variant
- Location
- chr3:129436765 (GRCh38)
- Gene constraint
- LOEUF 1.023 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.67 · 19 PDB
- Residue 293
- a UniProt-annotated variant site (in tpds2; no mbd4 protein detected by immunohistochemical analysis in patient tumor tissue); a UniProt-annotated variant site (in uvm1); a UniProt-annotated variant site (in tpds2)
Similar variants
- MBD4 p.Ala293Ser Uncertain significance ★★ ⚠ same residue
- MBD4 p.Ala293Val Uncertain significance ★ ⚠ same residue
- MBD4 c.1544-1G>A Likely pathogenic ★★ same condition
- MBD4 c.1544-1G>T Pathogenic/Likely pathogenic ★★ same condition
- MBD4 c.1544-2A>G Likely pathogenic ★★ same condition
- MBD4 c.335+1G>A Likely pathogenic ★★ same condition
- MBD4 p.Arg181Ter Pathogenic ★★ same condition
- MBD4 p.Arg400Ter 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/mbd4-p-ala293 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown