MBD4 p.Pro191=
c.573G>A · rs201684514 · VCV2873962
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00737%, nfe)
Conditions
2
Inborn genetic diseases
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 -0.24 | GERP -4.3, phastCons 0.001 |
| Overall | ||
| CADD | 7.286 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00737%
European (non-Finnish) · 87/1,179,890 alleles
Filtering AF
0.00605%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00565%
Overall
0.00613%
99/1,614,016 alleles · very rare
exomes 94/1,461,724 · genomes 5/152,292 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00737% | 13,562 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,626 |
| African / African-American | 0.00533% | 18,763 |
| East Asian | 0.00446% | 22,441 |
| Admixed American | 0.00167% | 60,022 |
| South Asian | 0.0011% | 91,076 |
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.Pro191=
- Coding
- c.573G>A
- MANE Select
- NM_001276270
- dbSNP
- rs201684514
- Type
- single nucleotide variant
- Location
- chr3:129437071 (GRCh38)
- Gene constraint
- LOEUF 1.023 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.67 · 19 PDB
- Residue 191
- 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.Pro191Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- MBD4 c.104+1G>A Likely pathogenic ★★ same condition
- 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-pro191 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown