Is MYO7A p.Arg1739= (c.5215C>A) pathogenic?

MYO7A p.Arg1739= (c.5215C>A) is classified Benign/Likely benign in MYO7A (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-31). Low-frequency (popmax 2.49%, afr); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Arg1739= (c.5215C>A)?

MYO7A p.Arg1739= (c.5215C>A) 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.Arg1739= (c.5215C>A) in the general population?

MYO7A p.Arg1739= (c.5215C>A) is low-frequency (popmax 2.49%, afr) (gnomAD).

How is Usher syndrome inherited?

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

MYO7A p.Arg1739=

c.5215C>A · rs111033477 · VCV43276

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.49%, afr)

Conditions

Usher syndrome type 1

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 6	GERP 1.8, phastCons 1
Overall
CADD	12.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.49% African / African-American · 1,824/73,118 alleles

Filtering AF 2.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.36%

Overall 0.13% 2,014/1,549,206 alleles · low-frequency exomes 966/1,396,894 · genomes 1,048/152,312 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.49%	40
Remaining individualsnot grpmax-eligible	0.162%	618
Admixed American	0.141%	709
Middle Eastern	0.0228%	4,386
European (non-Finnish)	0.00166%	60,374
South Asian	0.00119%	83,984

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.Arg1739=
Coding: c.5215C>A
MANE Select: NM_000260
dbSNP: rs111033477
Type: single nucleotide variant
Location: chr11:77203106 (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 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.Arg1739Ter Pathogenic ★★ same residue
MYO7A p.Arg1739Leu 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

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-arg1739 (accessed [today's date]).

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