Is MYO7A p.Gly1842fs (c.5515_5522dup) pathogenic?

MYO7A p.Gly1842fs (c.55155522dup) is classified Pathogenic in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-26). Very rare (popmax 0.000855%, nfe); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Gly1842fs (c.5515_5522dup)?

MYO7A p.Gly1842fs (c.5515_5522dup) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Gly1842fs (c.5515_5522dup) in the general population?

MYO7A p.Gly1842fs (c.5515_5522dup) is very rare (popmax 0.000855%, nfe) (gnomAD).

MYO7A p.Gly1842fs

c.5515_5522dup · rs762117246 · VCV2867955

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000855%, 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 40 of 49
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.7	GERP 1.3, phastCons 1
Overall
CADD	36.0	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 0.000855% European (non-Finnish) · 10/1,169,906 alleles

Filtering AF 0.000432% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000315%

Overall 0.000628% 10/1,591,612 alleles · very rare exomes 8/1,439,436 · genomes 2/152,176 · 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.Gly1842fs
Coding: c.5515_5522dup
MANE Select: NM_000260
dbSNP: rs762117246
Type: Duplication
Location: chr11:77205495 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1842: 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

Similar variants

MYO7A p.Glu1830fs Likely pathogenic ★★ same condition
MYO7A p.His133fs Pathogenic ★★ same condition
MYO7A p.Ile454fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Leu1046fs Pathogenic ★★ same condition
MYO7A p.Lys542fs Pathogenic ★★ same condition
MYO7A p.Pro1244fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Asp1613dup Uncertain significance ★★ same condition
MYO7A p.Gly1842= Likely benign ★★ same residue

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-gly1842fs (accessed [today's date]).

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