MAFB p.Arg249=
c.745C>A · rs561320614 · VCV338408
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0914%, eas)
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 6.3 | GERP 2.4, phastCons 1 |
| Overall | ||
| CADD | 14.48 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0914%
East Asian · 41/44,882 alleles
Filtering AF
0.0692%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0614%
Overall
0.00459%
74/1,613,720 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0914% | 1,095 |
| Remaining individualsnot grpmax-eligible | 0.0528% | 1,894 |
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.Arg249=
- Coding
- c.745C>A
- MANE Select
- NM_005461
- dbSNP
- rs561320614
- Type
- single nucleotide variant
- Location
- chr20:40688106 (GRCh38)
- Gene constraint
- LOEUF 0.469 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.87
- Residue 249
- the bzip domain; the 'basic motif' region
Similar variants
- MAFB p.Arg249Gly Likely 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
- MAFB p.Ala176Thr 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-arg249 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown