Is MYO7A p.Asp365fs (c.1091dup) pathogenic?

MYO7A p.Asp365fs (c.1091dup) is classified Pathogenic in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-12-19). Very rare (popmax 8.68e-05%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Asp365fs (c.1091dup)?

MYO7A p.Asp365fs (c.1091dup) is associated with autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Asp365fs (c.1091dup) in the general population?

MYO7A p.Asp365fs (c.1091dup) is very rare (popmax 8.68e-05%, nfe) (gnomAD).

MYO7A p.Asp365fs

c.1091dup · rs1952854443 · VCV1185626

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.68e-05%, nfe)

Conditions

autosomal recessive nonsyndromic hearing loss 2

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 11 of 49
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.7	GERP 1.6, phastCons 1
Overall
CADD	29.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.68e-05% European (non-Finnish) · 1/1,151,448 alleles

Overall 6.42e-05% 1/1,556,538 alleles · very rare exomes 0/1,404,786 · genomes 1/151,752 · 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.Asp365fs
Coding: c.1091dup
MANE Select: NM_000260
dbSNP: rs1952854443
Type: Duplication
Location: chr11:77160167 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 365: the myosin motor domain

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

Disease context

autosomal recessive nonsyndromic hearing loss 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Glu1830fs Likely pathogenic ★★ same condition
MYO7A p.His133fs Pathogenic ★★ same condition
MYO7A p.Leu1046fs Pathogenic ★★ same condition
MYO7A p.Lys542fs Pathogenic ★★ same condition
MYO7A p.Met283fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Pro1244fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ser611_Ser612insTer Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Tyr1396fs 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-asp365fs (accessed [today's date]).

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