MRTFB p.Ser975Pro
c.2923T>C · VCV4553414
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00534%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.191 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 6.1 | GERP 1.1, phastCons 1 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 43 kb · p 0.71 · regional, not allelic |
| Overall | ||
| CADD | 24.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00534%
African / African-American · 4/74,930 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.000372%
6/1,614,100 alleles · very rare
exomes 4/1,461,892 · genomes 2/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00534% | 18,732 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
| European (non-Finnish) | 8.47e-05% | 1,180,040 |
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.Ser975Pro
- Coding
- c.2923T>C
- MANE Select
- NM_001308142
- Type
- single nucleotide variant
- Location
- chr16:14261067 (GRCh38)
- Gene constraint
- LOEUF 0.351 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 53.38
Similar variants
- 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
- MRTFB p.Ala138Glu 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-ser975pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown