Is MYO7A p.Arg373= (c.1119C>T) pathogenic?

MYO7A p.Arg373= (c.1119C>T) is classified Uncertain significance in MYO7A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-05-09). Very rare (popmax 0.000172%, nfe); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Arg373= (c.1119C>T)?

MYO7A p.Arg373= (c.1119C>T) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Arg373= (c.1119C>T) in the general population?

MYO7A p.Arg373= (c.1119C>T) is very rare (popmax 0.000172%, nfe) (gnomAD).

MYO7A p.Arg373=

c.1119C>T · VCV4058122

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000172%, nfe)

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.044	GERP -0.53, phastCons 0.87
Overall
CADD	9.128	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000172% European (non-Finnish) · 2/1,162,742 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000127% 2/1,578,328 alleles · very rare exomes 2/1,425,996 · genomes 0/152,332 · 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.Arg373=
Coding: c.1119C>T
MANE Select: NM_000260
Type: single nucleotide variant
Location: chr11:77160201 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 373: the myosin motor 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.Arg373Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Arg373Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Arg373His Uncertain significance ★★ same residue
MYO7A p.Arg373Gly 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

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-arg373 (accessed [today's date]).

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