MYO7A p.Leu1469=
c.4407C>T · rs747856394 · VCV764712
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00731%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.22 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.36 | GERP -1.6, phastCons 0.079 |
| Overall | ||
| CADD | 13.97 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00731%
European (non-Finnish) · 86/1,175,670 alleles
Filtering AF
0.00606%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00559%
Overall
0.00542%
87/1,604,900 alleles · very rare
exomes 85/1,452,732 · genomes 2/152,168 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00731% | 13,671 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,182 |
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.Leu1469=
- Coding
- c.4407C>T
- MANE Select
- NM_000260
- dbSNP
- rs747856394
- Type
- single nucleotide variant
- Location
- chr11:77197564 (GRCh38)
- Gene constraint
- LOEUF 0.995 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.73 · 1 PDB
- Residue 1469
- the ferm 1 domain
Similar variants
- MYO7A p.Leu1469Phe Uncertain significance ★★ ⚠ same residue
- MYO7A p.Leu1469Val Uncertain significance ★ ⚠ 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-leu1469 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown