MRTFA p.Leu728=
c.2184G>A · rs140008214 · VCV1682987
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.171%, amr)
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 -0.1 | GERP 1.3 |
| Overall | ||
| CADD | 1.105 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.171%
Admixed American · 86/50,438 alleles
Filtering AF
0.141%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.131%
Overall
0.00826%
130/1,573,682 alleles · rare
exomes 92/1,421,436 · genomes 38/152,246 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.171% | 586 |
| Middle Eastern | 0.0171% | 5,832 |
| Remaining individualsnot grpmax-eligible | 0.0099% | 10,097 |
| East Asian | 0.00671% | 14,903 |
| European (non-Finnish) | 0.00283% | 35,299 |
| African / African-American | 0.00136% | 73,378 |
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
- MRTFA
- Protein
- p.Leu728=
- Coding
- c.2184G>A
- MANE Select
- NM_020831
- dbSNP
- rs140008214
- Type
- single nucleotide variant
- Location
- chr22:40418554 (GRCh38)
- Gene constraint
- LOEUF 0.389 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 56.59 · 2 PDB
- Residue 728
- the 'disordered' region; a UniProt-annotated variant site (in imd66; probable loss-of-function; patient's dendritic cells are morphologically distinct from control dendritic cells and show reduced spreading on fibronectin-coated coverslips, a marked reduction in total f-actin staining and a complete absence of podosomes, a similar phenotype to that of thp1 cells in which mrtfa was silenced)
Similar variants
- MRTFA p.Leu728Trp Uncertain significance ★ ⚠ same residue
- MRTFA p.Ala352Thr Uncertain significance ★★ ⚠ same type
- MRTFA p.Ala360Thr Uncertain significance ★★ ⚠ same type
- MRTFA p.Ala429Ser Uncertain significance ★★ ⚠ same type
- MRTFA p.Ala479Gly Uncertain significance ★★ ⚠ same type
- MRTFA p.Ala479Val Uncertain significance ★★ ⚠ same type
- MRTFA p.Ala534Thr Uncertain significance ★★ ⚠ same type
- MRTFA p.Ala537Val 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/mrtfa-p-leu728 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown