MBD4 p.Ser196=
c.588A>G · VCV4713331
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0022%, sas)
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 -0.96 | GERP -4.5 |
| Overall | ||
| CADD | 2.198 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
South Asian · 2/91,080 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000137%
Overall
0.000124%
2/1,614,220 alleles · very rare
exomes 2/1,461,880 · genomes 0/152,340 · 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.Ser196=
- Coding
- c.588A>G
- MANE Select
- NM_001276270
- Type
- single nucleotide variant
- Location
- chr3:129437056 (GRCh38)
- Gene constraint
- LOEUF 1.023 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.67 · 19 PDB
- Residue 196
- 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)
Similar variants
- MBD4 p.Ser196Ala Uncertain significance ★★ ⚠ same residue
- MBD4 p.Ser196Ter Pathogenic ★ same residue
- MBD4 p.Ser196Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- MBD4 p.Ser196Pro 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
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-ser196 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown