Is MYO7A p.Arg761= (c.2283G>A) pathogenic?

MYO7A p.Arg761= (c.2283G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-12-19). Rare (popmax 0.109%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Arg761= (c.2283G>A)?

MYO7A p.Arg761= (c.2283G>A) is associated with Inborn genetic diseases, hearing loss disorder, Usher syndrome type 1 (ClinVar).

How common is MYO7A p.Arg761= (c.2283G>A) in the general population?

MYO7A p.Arg761= (c.2283G>A) is rare (popmax 0.109%, nfe) (gnomAD).

MYO7A p.Arg761=

c.2283G>A · rs111033229 · VCV43179

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.109%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.5	GERP 0.54, phastCons 1
Overall
CADD	11.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.109% European (non-Finnish) · 1,276/1,175,462 alleles

Filtering AF 0.104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.102%

Overall 0.0842% 1,350/1,602,990 alleles · rare exomes 1,259/1,450,764 · genomes 91/152,226 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.109%	921
Remaining individualsnot grpmax-eligible	0.0709%	1,411
Middle Eastern	0.0329%	3,035
African / African-American	0.0227%	4,397
East Asian	0.0135%	7,417
Admixed American	0.00679%	14,736
South Asian	0.00113%	88,818

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.Arg761=
Coding: c.2283G>A
MANE Select: NM_000260
dbSNP: rs111033229
Type: single nucleotide variant
Location: chr11:77179045 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 761: the iq 1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

MYO7A p.Arg761Ser Uncertain significance ★ ⚠ same residue
MYO7A p.Arg761fs 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

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-arg761 (accessed [today's date]).

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