MRTFA p.665AP[2]
c.1993GCCCCC[2] · rs754085988 · VCV1043564
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.11%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.5 | GERP -0.84, phastCons 0.067 |
| Overall | ||
| CADD | 1.091 | PHRED · no single calibrated threshold — expert panels disagree |
| Region caveats | ||
| Repeat context | tandem | G-rich low complexity · ambiguous alignment · confidence, not pathogenicity |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.11%
South Asian · 822/74,342 alleles
Filtering AF
1.04%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.02%
Overall
0.131%
1,922/1,471,034 alleles · low-frequency
exomes 1,425/1,319,324 · genomes 497/151,710 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.11% | 90 |
| African / African-American | 1.02% | 98 |
| Remaining individualsnot grpmax-eligible | 0.144% | 697 |
| Admixed American | 0.0745% | 1,342 |
| Middle Eastern | 0.0723% | 1,383 |
| European (non-Finnish) | 0.0236% | 4,240 |
| East Asian | 0.00739% | 13,528 |
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.665AP[2]
- Coding
- c.1993GCCCCC[2]
- MANE Select
- NM_020831
- dbSNP
- rs754085988
- Type
- Microsatellite
- Location
- chr22:40418728 (GRCh38)
- Gene constraint
- LOEUF 0.389 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 56.59 · 2 PDB
Similar variants
- MRTFA p.Gln381dup Uncertain significance ★★ same type
- MRTFA p.665AP[1] Uncertain significance ★ same type
- MRTFA p.Gln367_Leu368insGln Uncertain significance ★ same type
- MRTFA p.Gln381_His382insGlnGln Uncertain significance ★ same type
- MRTFA p.Gln381del Uncertain significance ★ same type
- MRTFA p.Glu601del Uncertain significance ★ same type
- MRTFA p.His383del Uncertain significance ★ same type
- MRTFA p.His383dup 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-665ap-2 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown