Is MYO7A p.Ile195fs (c.582del) pathogenic?

MYO7A p.Ile195fs (c.582del) is classified Pathogenic in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-25). Very rare (popmax 8.48e-05%, nfe); Associated with Rare genetic deafness.

What condition is associated with MYO7A p.Ile195fs (c.582del)?

MYO7A p.Ile195fs (c.582del) is associated with Rare genetic deafness (ClinVar).

How common is MYO7A p.Ile195fs (c.582del) in the general population?

MYO7A p.Ile195fs (c.582del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

MYO7A p.Ile195fs

c.582del · rs111033238 · VCV43301

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Rare genetic deafness

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 49
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,868 alleles

Overall 6.2e-05% 1/1,613,834 alleles · very rare exomes 1/1,461,678 · genomes 0/152,156 · joint denominator

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.Ile195fs
Coding: c.582del
MANE Select: NM_000260
dbSNP: rs111033238
Type: Deletion
Location: chr11:77156767 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 195: the myosin motor domain

Full MYO7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Rare genetic deafness — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Gln1178fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.His1355fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ile325fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Lys725fs Pathogenic ★★ same condition
MYO7A p.Val1519fs Pathogenic ★★ same condition
MYO7A c.(?_6355 Pathogenic ★ same condition
MYO7A p.His1109fs Pathogenic ★ same condition
MYO7A c.1200+1G>A Pathogenic/Likely pathogenic ★★ same condition

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-ile195fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown