Is MYO7A p.Glu968= (c.2904G>A) pathogenic?

MYO7A p.Glu968= (c.2904G>A) is classified Pathogenic/Likely pathogenic in MYO7A (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-08-11). Absent from gnomAD v4.1; Associated with MYO7A-related disorder.

What condition is associated with MYO7A p.Glu968= (c.2904G>A)?

MYO7A p.Glu968= (c.2904G>A) is associated with MYO7A-related disorder, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Glu968= (c.2904G>A) in the general population?

MYO7A p.Glu968= (c.2904G>A) is absent from gnomAD v4.1 (gnomAD).

MYO7A p.Glu968=

c.2904G>A · rs111033233 · VCV228280

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

MYO7A-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.94	donor loss · deltas
Pangolin	Δ0.82	loss · gain 0.57 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MYO7A
Protein: p.Glu968=
Coding: c.2904G>A
MANE Select: NM_000260
dbSNP: rs111033233
Type: single nucleotide variant
Location: chr11:77181589 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 968: a UniProt-annotated variant site (in ush1b)

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

Disease context

MYO7A-related disorder

Also linked: Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 2 autosomal dominant nonsyndromic hearing loss 11 Usher syndrome type 1B

Similar variants

MYO7A p.Glu968Asp Likely pathogenic ★★★ ⚠ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same condition
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same condition
MYO7A p.Arg668Cys Pathogenic ★★★ same condition
MYO7A p.Arg853His Likely pathogenic ★★★ same condition
MYO7A p.Gly2187Asp 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-glu968 (accessed [today's date]).

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