Is MYO7A p.Gly34fs (c.99_100del) pathogenic?

MYO7A p.Gly34fs (c.99100del) is classified Pathogenic/Likely pathogenic in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-06). Ultra-rare (popmax 0.0147%, afr); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Gly34fs (c.99_100del)?

MYO7A p.Gly34fs (c.99_100del) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Gly34fs (c.99_100del) in the general population?

MYO7A p.Gly34fs (c.99_100del) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

MYO7A p.Gly34fs

c.99_100del · rs782312060 · VCV945193

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

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 3 of 49
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.3, phastCons 1
Overall
CADD	35.0	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 0.0147% African / African-American · 11/74,892 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.000745% 12/1,610,520 alleles · ultra-rare exomes 5/1,458,340 · genomes 7/152,180 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,808
Admixed American	0.00168%	59,590

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.Gly34fs
Coding: c.99_100del
MANE Select: NM_000260
dbSNP: rs782312060
Type: Deletion
Location: chr11:77142789 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB

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 c.3503+12_3503+33del Benign ★★★ same condition
MYO7A c.2283-2_2293del Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.5471_5480+5del Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala2009fs Pathogenic ★★ same condition
MYO7A p.Ala353_Thr354insTer Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala743fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Asp2076fs Pathogenic ★★ same condition
MYO7A p.Asp521fs 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-gly34fs (accessed [today's date]).

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