Is MYO7A p.Lys1753fs (c.5259del) pathogenic?

MYO7A p.Lys1753fs (c.5259del) is classified Pathogenic/Likely pathogenic in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-19). Very rare (popmax 0.000174%, nfe); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Lys1753fs (c.5259del)?

MYO7A p.Lys1753fs (c.5259del) is associated with Usher syndrome type 1B, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Lys1753fs (c.5259del) in the general population?

MYO7A p.Lys1753fs (c.5259del) is very rare (popmax 0.000174%, nfe) (gnomAD).

MYO7A p.Lys1753fs

c.5259del · rs1555103532 · VCV556062

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000174%, nfe)

Conditions

Usher syndrome type 1B

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 38 of 49
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.1	GERP -0.36, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000174% European (non-Finnish) · 2/1,148,060 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000129% 2/1,551,078 alleles · very rare exomes 2/1,398,716 · genomes 0/152,362 · 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.Lys1753fs
Coding: c.5259del
MANE Select: NM_000260
dbSNP: rs1555103532
Type: Deletion
Location: chr11:77203150 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1753: the myth4 2 domain

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

Disease context

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

Also linked: Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 2

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 c.5471_5480+5del 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.Ala353_Thr354insTer 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-lys1753fs (accessed [today's date]).

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