Is MYO7A p.Arg336fs (c.1005_1012delinsTGCCAACAGC…[40 bp]) pathogenic?

MYO7A p.Arg336fs (c.10051012delinsTGCCAACAGC…[40 bp]) is classified Pathogenic/Likely pathogenic in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-08). Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Arg336fs (c.1005_1012delinsTGCCAACAGC…[40 bp])?

MYO7A p.Arg336fs (c.1005_1012delinsTGCCAACAGC…[40 bp]) is associated with Usher syndrome type 1B, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

MYO7A p.Arg336fs

c.1005_1012delinsTGCCAACAGC…[40 bp] · VCV3574009

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 10 of 49
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.51	GERP -0.71, phastCons 0.024

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

Variant & gene context

Gene: MYO7A
Protein: p.Arg336fs
Coding: c.1005_1012delinsTGCCAACAGCCCCTTGCTGCCTCCCCTGATGCTGTGCCCC
MANE Select: NM_000260
Type: Indel
Location: chr11:77159448 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 336: the myosin motor 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 autosomal dominant nonsyndromic hearing loss 11

Similar variants

MYO7A p.Arg336His Likely benign ★★★ ⚠ same residue
MYO7A p.Arg336Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A c.1798-7_1800delinsATCGGCTGCT Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.3503+1_3503+12delinsC Likely pathogenic ★★ same condition
MYO7A p.Glu1515_Met1517delinsAla Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala2083fs Likely pathogenic ★ same condition
MYO7A p.Asp992fs Pathogenic ★ same condition
MYO7A p.Gly1191fs 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-arg336fs (accessed [today's date]).

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