MRTFA p.Leu813=
c.2439C>G · rs758122207 · VCV2997602
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.043%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.1 | GERP -4.2 |
| Overall | ||
| CADD | 0.928 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.043%
Middle Eastern · 2/4,652 alleles
Filtering AF
0.00755%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00312%
Overall
0.00298%
48/1,610,292 alleles · ultra-rare
exomes 45/1,457,986 · genomes 3/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.043% | 2,326 |
| European (non-Finnish) | 0.00365% | 27,425 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,144 |
| African / African-American | 0.00133% | 74,968 |
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.Leu813=
- Coding
- c.2439C>G
- MANE Select
- NM_020831
- dbSNP
- rs758122207
- Type
- single nucleotide variant
- Location
- chr22:40417419 (GRCh38)
- Gene constraint
- LOEUF 0.389 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 56.59 · 2 PDB
- Residue 813
- 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.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
- MRTFA p.Ala616Val 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-leu813 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown