Is MYO7A p.Arg933His (c.2798G>A) pathogenic?

MYO7A p.Arg933His (c.2798G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 14 submitters; last evaluated 2026-03-16). AlphaMissense: likely benign (0.1218); Ultra-rare (popmax 0.0392%, nfe); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Arg933His (c.2798G>A)?

MYO7A p.Arg933His (c.2798G>A) is associated with Usher syndrome type 1, hearing loss disorder, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Arg933His (c.2798G>A) in the general population?

MYO7A p.Arg933His (c.2798G>A) is ultra-rare (popmax 0.0392%, 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.Arg933His (c.2798G>A)?

AlphaMissense predicts likely benign (score 0.1218) — an in-silico prediction, not a clinical call.

MYO7A p.Arg933His

c.2798G>A · rs201489714 · VCV229004

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.1218 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0392%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Usher syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.1218	likely benign
REVEL	0.477	indeterminate
SaProt	LLR -8.78	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.9	GERP 0.64, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	27.7	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 0.0392% European (non-Finnish) · 462/1,179,728 alleles

Filtering AF 0.0362% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.035%

Overall 0.0311% 501/1,612,888 alleles · ultra-rare exomes 459/1,460,656 · genomes 42/152,232 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0392%	2,554
Remaining individualsnot grpmax-eligible	0.032%	3,121
Middle Eastern	0.0164%	6,082
Admixed American	0.0133%	7,492
African / African-American	0.00934%	10,705
South Asian	0.0022%	45,467
Finnishnot grpmax-eligible	0.00158%	63,452

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.Arg933His
Coding: c.2798G>A
MANE Select: NM_000260
dbSNP: rs201489714
Type: single nucleotide variant
Location: chr11:77181483 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 933: the 'sah' region

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: hearing loss disorder 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.Arg933Cys 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-arg933his (accessed [today's date]).

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