MRTFB p.Met522Arg
c.1565T>G · rs533601723 · VCV3210181
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00134%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.208 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 6.2 | GERP 0.3, phastCons 1 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 43 kb · p 0.71 · regional, not allelic |
| Overall | ||
| CADD | 22.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00134%
African / African-American · 1/74,870 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000248%
4/1,612,596 alleles · very rare
exomes 2/1,460,562 · genomes 2/152,034 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00134% | 74,870 |
| European (non-Finnish) | 0.000254% | 393,335 |
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
- MRTFB
- Protein
- p.Met522Arg
- Coding
- c.1565T>G
- MANE Select
- NM_001308142
- dbSNP
- rs533601723
- Type
- single nucleotide variant
- Location
- chr16:14246825 (GRCh38)
- Gene constraint
- LOEUF 0.351 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 53.38
Similar variants
- MRTFB p.Met522Val Uncertain significance ★ same residue
- MRTFB p.Asn47= Benign/Likely benign ★★ same type
- MRTFB p.Ser643= Benign ★★ same type
- MRTFB p.Thr9= Benign ★★ same type
- MRTFB p.Ala91Pro Pathogenic ★ same type
- MRTFB p.Leu160Pro Likely pathogenic ★ same type
- MRTFB c.693+1G>T Uncertain significance ★ same type
- MRTFB p.Ala1080Val Uncertain significance ★ 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/mrtfb-p-met522arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown