MRTFA p.Pro734=
c.2202G>A · rs561837303 · VCV1682984
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
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. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -8.4 | GERP -4.3 |
| Overall | ||
| CADD | 0.523 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0201%
East Asian · 9/44,762 alleles
Filtering AF
0.0104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00964%
Overall
0.0114%
180/1,585,500 alleles · ultra-rare
exomes 169/1,433,304 · genomes 11/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0201% | 4,974 |
| Admixed American | 0.0154% | 6,497 |
| South Asian | 0.0138% | 7,251 |
| Remaining individualsnot grpmax-eligible | 0.0131% | 7,638 |
| European (non-Finnish) | 0.0119% | 8,416 |
| African / African-American | 0.00407% | 24,588 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00366% | 27,336 |
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.Pro734=
- Coding
- c.2202G>A
- MANE Select
- NM_020831
- dbSNP
- rs561837303
- Type
- single nucleotide variant
- Location
- chr22:40418536 (GRCh38)
- Gene constraint
- LOEUF 0.389 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 56.59 · 2 PDB
- Residue 734
- 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.Pro734Ser Benign ★★ same residue
- MRTFA p.Pro734Ala Uncertain significance ★ ⚠ same residue
- MRTFA p.Pro734Leu Conflicting classifications of pathogenicity ★ ⚠ 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
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-pro734 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown