MRTFA p.Arg131His
c.392G>A · VCV4553402
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5849 | likely pathogenic |
|---|---|---|
| REVEL | 0.804 | moderately pathogenic-leaning |
| SaProt | LLR -12.95 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 2.6, phastCons 1 |
| Regional constraint | o/e 0.51 | unconstrained · MANE · 128 kb · p 2.9e-11 · regional, not allelic |
| Overall | ||
| CADD | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R31H vs ClinVar R131H) — verify the residue.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.00625% | 16,002 |
| East Asiangrpmax | 0.00223% | 44,888 |
| African / African-American | 0.00133% | 74,924 |
| South Asian | 0.0011% | 91,086 |
| European (non-Finnish) | 0.000339% | 294,995 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Arg131His
- Coding
- c.392G>A
- MANE Select
- NM_020831
- Type
- single nucleotide variant
- Location
- chr22:40431452 (GRCh38)
- Gene constraint
- LOEUF 0.389 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 56.59 · 2 PDB
- Residue 31 UniProt numbering
- the 'mediates interaction with scai and actb' region
Similar variants
- MRTFA p.Arg131Cys Uncertain significance ★ ⚠ same residue
- MRTFA p.Arg131Leu 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
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-arg131his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown