MRTFA p.Pro958=
c.2874G>A · rs538107883 · VCV1139999
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0989%, sas)
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 -7.6 | GERP -5.1 |
| Overall | ||
| CADD | 5.563 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0989%
South Asian · 90/91,004 alleles
Filtering AF
0.0824%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0762%
Overall
0.00676%
109/1,613,598 alleles · ultra-rare
exomes 93/1,461,348 · genomes 16/152,250 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0989% | 1,011 |
| Admixed American | 0.00333% | 29,998 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,247 |
| African / African-American | 0.00267% | 37,511 |
| European (non-Finnish) | 0.0011% | 90,766 |
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.Pro958=
- Coding
- c.2874G>A
- MANE Select
- NM_020831
- dbSNP
- rs538107883
- Type
- single nucleotide variant
- Location
- chr22:40411612 (GRCh38)
- Gene constraint
- LOEUF 0.389 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 56.59 · 2 PDB
Similar variants
- MRTFA p.Pro958Leu Uncertain significance ★★ ⚠ same residue
- MRTFA p.Pro958Ala Uncertain significance ★ ⚠ same residue
- MRTFA p.Pro958Gln Uncertain significance ★ ⚠ same residue
- MRTFA p.Pro958Ser 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
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-pro958 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown