Is MYO7A p.Gly229= (c.687C>T) pathogenic?

MYO7A p.Gly229= (c.687C>T) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-02-02). Ultra-rare (popmax 0.0587%, nfe); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Gly229= (c.687C>T)?

MYO7A p.Gly229= (c.687C>T) is associated with Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.Gly229= (c.687C>T) in the general population?

MYO7A p.Gly229= (c.687C>T) is ultra-rare (popmax 0.0587%, nfe) (gnomAD).

How is Usher syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MYO7A p.Gly229=

c.687C>T · rs371142158 · VCV43339

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0587%, nfe)

Conditions

Usher syndrome type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.26	donor gain · deltas
Constraint at this position
Conservation	phyloP -20	GERP -3.8
Overall
CADD	5.502	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0587% European (non-Finnish) · 693/1,179,904 alleles

Filtering AF 0.0551% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0537%

Overall 0.0459% 741/1,613,826 alleles · ultra-rare exomes 689/1,461,584 · genomes 52/152,242 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0587%	1,703
Admixed American	0.0467%	2,143
Remaining individualsnot grpmax-eligible	0.0192%	5,205
African / African-American	0.008%	12,493
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
South Asian	0.0011%	91,090

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.Gly229=
Coding: c.687C>T
MANE Select: NM_000260
dbSNP: rs371142158
Type: single nucleotide variant
Location: chr11:77156956 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 229: the myosin motor domain

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

Disease context

Usher syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

MYO7A p.Gly229Ser Uncertain significance ★ ⚠ 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.Glu968Asp 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-gly229 (accessed [today's date]).

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