MRTFA p.Pro257=
c.771C>G · rs2052904563 · VCV1964302
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0182%, mid)
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 -0.93 | GERP -5.1 |
| Overall | ||
| CADD | 4.955 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0182%
Middle Eastern · 1/5,494 alleles
Overall
0.000188%
3/1,597,296 alleles · ultra-rare
exomes 3/1,444,920 · genomes 0/152,376 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0182% | 5,494 |
| Remaining individualsnot grpmax-eligible | 0.00162% | 61,692 |
| European (non-Finnish) | 8.52e-05% | 1,173,422 |
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.Pro257=
- Coding
- c.771C>G
- MANE Select
- NM_020831
- dbSNP
- rs2052904563
- Type
- single nucleotide variant
- Location
- chr22:40424212 (GRCh38)
- Gene constraint
- LOEUF 0.389 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 56.59 · 2 PDB
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-pro257 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown