MRTFA p.Arg621=
c.1863C>T · rs772288792 · VCV2966883
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, 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 -9.6 | GERP -5.1 |
| Overall | ||
| CADD | 0.161 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
East Asian · 6/44,856 alleles
Filtering AF
0.00579%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00394%
Overall
0.00267%
43/1,612,358 alleles · ultra-rare
exomes 40/1,460,230 · genomes 3/152,128 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0134% | 7,476 |
| African / African-American | 0.00935% | 10,699 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,821 |
| South Asian | 0.00329% | 30,358 |
| European (non-Finnish) | 0.00195% | 51,297 |
| Admixed American | 0.00167% | 59,954 |
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.Arg621=
- Coding
- c.1863C>T
- MANE Select
- NM_020831
- dbSNP
- rs772288792
- Type
- single nucleotide variant
- Location
- chr22:40418875 (GRCh38)
- Gene constraint
- LOEUF 0.389 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 56.59 · 2 PDB
Similar variants
- MRTFA p.Arg621Cys Uncertain significance ★★ ⚠ same residue
- MRTFA p.Arg621His 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-arg621 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown