MAFB p.Pro63=
c.189G>A · rs201590858 · VCV338412
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00864%, nfe)
Conditions
1
multicentric carpo-tarsal osteolysis with or without nephropathy
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 -3.8 | GERP -4.8 |
| Overall | ||
| CADD | 8.532 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00864%
European (non-Finnish) · 102/1,179,930 alleles
Filtering AF
0.00724%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00676%
Overall
0.00669%
108/1,613,860 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00864% | 11,568 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,826 |
| Admixed American | 0.00167% | 60,004 |
| African / African-American | 0.00133% | 74,924 |
| South Asian | 0.0011% | 91,090 |
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
- MAFB
- Protein
- p.Pro63=
- Coding
- c.189G>A
- MANE Select
- NM_005461
- dbSNP
- rs201590858
- Type
- single nucleotide variant
- Location
- chr20:40688662 (GRCh38)
- Gene constraint
- LOEUF 0.469 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.87
- Residue 63
- a UniProt-annotated variant site (in mcto); the 'disordered' region
Similar variants
- MAFB p.Pro63Leu Pathogenic ★★ same residue
- MAFB p.Pro63Ser Pathogenic ★ same residue
- MAFB p.Pro59Leu Pathogenic/Likely pathogenic ★★ same condition
- MAFB p.Ser54Leu Pathogenic ★★ ⚠ same condition
- MAFB p.Ser70Leu Pathogenic/Likely pathogenic ★★ same condition
- MAFB p.Thr62Ala Pathogenic ★★ same condition
- MAFB c.-77C>G Uncertain significance ★★ same condition
- MAFB p.Ala110Glu Uncertain significance ★★ ⚠ 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/mafb-p-pro63 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown