MBD4 p.Ala103=
c.309A>G · rs2072493912 · VCV2698198
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00017%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.75 | GERP -3.6, phastCons 0.018 |
| Overall | ||
| CADD | 8.758 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00017%
European (non-Finnish) · 2/1,179,826 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000124%
2/1,613,964 alleles · very rare
exomes 2/1,461,628 · genomes 0/152,336 · 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.Ala103=
- Coding
- c.309A>G
- MANE Select
- NM_001276270
- dbSNP
- rs2072493912
- Type
- single nucleotide variant
- Location
- chr3:129437746 (GRCh38)
- Gene constraint
- LOEUF 1.023 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.67 · 19 PDB
- Residue 103
- the mbd domain; a UniProt-annotated variant site (in tpds2; no mbd4 protein detected by immunohistochemical analysis in patient tumor tissue); a turn
Similar variants
- MBD4 p.Ala103Gly Uncertain significance ★★ ⚠ same residue
- MBD4 p.Ala103Val Uncertain significance ★★ ⚠ same residue
- MBD4 c.104+1G>A Likely pathogenic ★★ same type
- MBD4 c.1544-1G>A Likely pathogenic ★★ same type
- MBD4 c.1544-1G>T Pathogenic/Likely pathogenic ★★ same type
- MBD4 c.1544-2A>G Likely pathogenic ★★ same type
- MBD4 c.335+1G>A Likely pathogenic ★★ same type
- MBD4 p.Arg181Ter 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/mbd4-p-ala103 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown