MRTFA p.Pro719=
c.2157G>A · rs372005183 · VCV1682991
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.053%, 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 -8.5 | GERP -4.5 |
| Overall | ||
| CADD | 0.401 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.053%
South Asian · 42/79,244 alleles
Filtering AF
0.0403%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0358%
Overall
0.0143%
222/1,550,012 alleles · ultra-rare
exomes 203/1,397,808 · genomes 19/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.053% | 1,887 |
| East Asian | 0.0449% | 2,228 |
| Remaining individualsnot grpmax-eligible | 0.0302% | 3,316 |
| Admixed American | 0.0232% | 4,306 |
| European (non-Finnish) | 0.0107% | 9,315 |
| Finnishnot grpmax-eligible | 0.0083% | 12,049 |
| African / African-American | 0.00275% | 36,347 |
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.Pro719=
- Coding
- c.2157G>A
- MANE Select
- NM_020831
- dbSNP
- rs372005183
- Type
- single nucleotide variant
- Location
- chr22:40418581 (GRCh38)
- Gene constraint
- LOEUF 0.389 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 56.59 · 2 PDB
- Residue 719
- the 'disordered' region
Similar variants
- MRTFA p.Pro719Leu 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
- MRTFA p.Ala537Val 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-pro719 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown