MRTFB p.Pro254Arg
c.761C>G · rs138935730 · VCV3210275
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0201%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.063 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 1.8 | GERP 1.1, phastCons 0.003 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 43 kb · p 0.71 · regional, not allelic |
| Overall | ||
| CADD | 7.671 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0201%
East Asian · 9/44,880 alleles
Filtering AF
0.0105%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00981%
Overall
0.0103%
167/1,614,164 alleles · ultra-rare
exomes 155/1,461,866 · genomes 12/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0201% | 4,987 |
| European (non-Finnish) | 0.0121% | 8,252 |
| Admixed American | 0.01% | 10,004 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,418 |
| African / African-American | 0.00267% | 37,517 |
| Finnishnot grpmax-eligible | 0.00156% | 64,034 |
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.Pro254Arg
- Coding
- c.761C>G
- MANE Select
- NM_001308142
- dbSNP
- rs138935730
- Type
- single nucleotide variant
- Location
- chr16:14234213 (GRCh38)
- Gene constraint
- LOEUF 0.351 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 53.38
- Residue 254
- the 'disordered' region
Similar variants
- MRTFB p.Pro254Gln 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-pro254arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown