MYO7A p.Pro1243=
c.3729G>A · rs727504023 · VCV167313
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00939%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -11 | GERP -3.5 |
| Overall | ||
| CADD | 0.682 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00939%
East Asian · 4/42,586 alleles
Filtering AF
0.00319%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00187%
Overall
0.00191%
30/1,571,016 alleles · very rare
exomes 23/1,418,766 · genomes 7/152,250 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00939% | 10,646 |
| African / African-American | 0.00541% | 18,497 |
| Remaining individualsnot grpmax-eligible | 0.00328% | 30,443 |
| Admixed American | 0.00187% | 53,406 |
| European (non-Finnish) | 0.00155% | 64,372 |
| South Asian | 0.00117% | 85,294 |
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
- MYO7A
- Protein
- p.Pro1243=
- Coding
- c.3729G>A
- MANE Select
- NM_000260
- dbSNP
- rs727504023
- Type
- single nucleotide variant
- Location
- chr11:77190118 (GRCh38)
- Gene constraint
- LOEUF 0.995 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.73 · 1 PDB
- Residue 1243
- the myth4 1 domain
Similar variants
- MYO7A p.Pro1243Leu Pathogenic/Likely pathogenic ★★ same residue
- MYO7A p.Pro1243Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
- MYO7A p.Pro1243Arg Pathogenic/Likely pathogenic same residue
- MYO7A p.Ala1288Pro Likely pathogenic ★★★ same type
- MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same type
- MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same type
- MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same type
- MYO7A p.Arg668Cys Pathogenic ★★★ 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/myo7a-p-pro1243 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown