Is MYO7A p.Leu1804fs (c.5411del) pathogenic?

MYO7A p.Leu1804fs (c.5411del) is classified Pathogenic in MYO7A (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-17). No allele count reported in gnomAD v4.1 (AN 1,593,848); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Leu1804fs (c.5411del)?

MYO7A p.Leu1804fs (c.5411del) is associated with Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Leu1804fs (c.5411del) in the general population?

MYO7A p.Leu1804fs (c.5411del) is no allele count reported in gnomAD v4.1 (AN 1,593,848) (gnomAD).

How is Usher syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MYO7A p.Leu1804fs

c.5411del · rs2497682974 · VCV3236335

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,593,848)

Conditions

Usher syndrome type 1

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 39 of 49
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP -0.6, phastCons 0.79

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,593,848). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MYO7A
Protein: p.Leu1804fs
Coding: c.5411del
MANE Select: NM_000260
dbSNP: rs2497682974
Type: Deletion
Location: chr11:77204160 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1804: the myth4 2 domain; an α-helix

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

Disease context

Usher syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive nonsyndromic hearing loss 2

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

MYO7A c.3503+12_3503+33del Benign ★★★ same condition
MYO7A c.2187+2_2187+8del Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.2283-2_2293del Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1277fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala2009fs Pathogenic ★★ same condition
MYO7A p.Ala202fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Asn769fs Pathogenic ★★ same condition
MYO7A p.Asp1613fs 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-leu1804fs (accessed [today's date]).

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