Is MYO7A p.Arg302His (c.905G>A) pathogenic?

MYO7A p.Arg302His (c.905G>A) is classified Likely benign in MYO7A (ClinVar, Expert panel, 14 submitters; last evaluated 2018-10-22). AlphaMissense: likely benign (0.1105); Rare (popmax 0.366%, nfe); Associated with Usher syndrome.

What condition is associated with MYO7A p.Arg302His (c.905G>A)?

MYO7A p.Arg302His (c.905G>A) is associated with Usher syndrome, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Arg302His (c.905G>A) in the general population?

MYO7A p.Arg302His (c.905G>A) is rare (popmax 0.366%, nfe) (gnomAD).

How is Usher syndrome inherited?

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

What do computational predictors say about MYO7A p.Arg302His (c.905G>A)?

AlphaMissense predicts likely benign (score 0.1105) — an in-silico prediction, not a clinical call.

MYO7A p.Arg302His

c.905G>A · rs41298135 · VCV11852

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.1105 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.366%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome

ClinGen expert panel — Hearing Loss VCEP

Likely Benign for Usher syndrome. Applied ACMG criteria (verbatim):

BS1 BP2 BS3_Supporting

Curation rationale (ClinGen, verbatim)

The filtering allele frequency of the c.905G>A (p.Arg302His) variant in the MYO7A gene is 0.4% for European chromosomes by gnomAD (587/126276 with 95% CI), which is a high enough frequency to be classified as likely benign based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BS1). While this variant has been reported in several individuals with Usher syndrome, in 2 individuals it was identified in cis with another pathogenic MYO7A variant (BP2; PMID 8900236). This variant has also been reported in at least 2 additional individuals with Usher syndrome who had alternate genetic etiologies identified (PMID: 25468891). In addition, in vitro functional evidence from one study suggests that the Arg302His variant had little effect on motor activity of MYO7A (BS3_Supporting PMID: 18700726). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel : BS1, BP2, BS3_Supporting.

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

Computational evidence

Protein change
AlphaMissense	0.1105	likely benign
REVEL	0.669	pathogenic-leaning
SaProt	LLR -8.81	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.366% European (non-Finnish) · 4,317/1,179,538 alleles

Filtering AF 0.357% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.353%

Overall 0.294% 4,747/1,613,070 alleles · rare exomes 4,440/1,460,784 · genomes 307/152,286 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.366%	273
Finnishnot grpmax-eligible	0.306%	327
Remaining individualsnot grpmax-eligible	0.208%	480
Middle Eastern	0.0826%	1,211
Ashkenazi Jewishnot grpmax-eligible	0.0777%	1,286
African / African-American	0.0653%	1,531
Admixed American	0.04%	2,500
South Asian	0.0044%	22,744

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.Arg302His
Coding: c.905G>A
MANE Select: NM_000260
dbSNP: rs41298135
Type: single nucleotide variant
Location: chr11:77158332 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 302: the myosin motor domain; a UniProt-annotated variant site (in)

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

Disease context

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

Also linked: Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 2 autosomal dominant nonsyndromic hearing loss 11 inherited retinal dystrophy 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.Arg302Gly Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg302Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Arg302Leu 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

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-arg302his (accessed [today's date]).

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