MYO7A p.Pro1221=
c.3663C>T · rs34864003 · VCV1123713
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0178%, mid)
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 -8.3 | GERP -3.5 |
| Overall | ||
| CADD | 0.975 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0178%
Middle Eastern · 1/5,614 alleles
Filtering AF
0.00188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00102%
Overall
0.00115%
18/1,567,990 alleles · ultra-rare
exomes 16/1,415,644 · genomes 2/152,346 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0178% | 5,614 |
| East Asian | 0.00708% | 14,125 |
| Finnishnot grpmax-eligible | 0.00167% | 60,046 |
| European (non-Finnish) | 0.00112% | 89,003 |
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.Pro1221=
- Coding
- c.3663C>T
- MANE Select
- NM_000260
- dbSNP
- rs34864003
- Type
- single nucleotide variant
- Location
- chr11:77190052 (GRCh38)
- Gene constraint
- LOEUF 0.995 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.73 · 1 PDB
- Residue 1221
- the myth4 1 domain
Similar variants
- MYO7A p.Pro1221Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
- MYO7A p.Pro1221fs 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
- MYO7A p.Arg853His Likely 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-pro1221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown