MRTFB p.Leu644Phe
c.1930C>T · rs145643612 · VCV3210201
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0893%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.102 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 2.3 | GERP 0.54, phastCons 0.14 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 43 kb · p 0.71 · regional, not allelic |
| Overall | ||
| CADD | 14.62 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0893%
African / African-American · 67/75,058 alleles
Filtering AF
0.0721%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0658%
Overall
0.00527%
85/1,614,162 alleles · ultra-rare
exomes 38/1,461,842 · genomes 47/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0893% | 1,120 |
| Admixed American | 0.0133% | 7,502 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,418 |
| European (non-Finnish) | 0.000339% | 295,009 |
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.Leu644Phe
- Coding
- c.1930C>T
- MANE Select
- NM_001308142
- dbSNP
- rs145643612
- Type
- single nucleotide variant
- Location
- chr16:14247190 (GRCh38)
- Gene constraint
- LOEUF 0.351 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 53.38
- Residue 644
- the 'disordered' region
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-leu644phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown