Is MYO7A p.Arg292Gln (c.875G>A) pathogenic?

MYO7A p.Arg292Gln (c.875G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-03). AlphaMissense: likely benign (0.232); Rare (popmax 0.179%, sas); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Arg292Gln (c.875G>A)?

MYO7A p.Arg292Gln (c.875G>A) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Arg292Gln (c.875G>A) in the general population?

MYO7A p.Arg292Gln (c.875G>A) is rare (popmax 0.179%, sas) (gnomAD).

What do computational predictors say about MYO7A p.Arg292Gln (c.875G>A)?

AlphaMissense predicts likely benign (score 0.232) — an in-silico prediction, not a clinical call.

MYO7A p.Arg292Gln

c.875G>A · rs535205981 · VCV749269

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.232 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.179%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
AlphaMissense	0.232	likely benign
REVEL	0.65	pathogenic-leaning
SaProt	LLR -11.66	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.7	GERP 0.64, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	27.4	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 0.179% South Asian · 162/90,558 alleles

Filtering AF 0.156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.148%

Overall 0.0109% 176/1,609,344 alleles · rare exomes 158/1,457,060 · genomes 18/152,284 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.179%	559
Middle Eastern	0.0166%	6,034
Remaining individualsnot grpmax-eligible	0.00482%	20,759
Admixed American	0.00334%	29,900
African / African-American	0.00133%	74,954
European (non-Finnish)	0.000595%	168,139

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.Arg292Gln
Coding: c.875G>A
MANE Select: NM_000260
dbSNP: rs535205981
Type: single nucleotide variant
Location: chr11:77158302 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 292: 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.Arg292= Likely benign ★★ same residue
MYO7A p.Arg292Leu Uncertain significance ★ ⚠ same residue
MYO7A p.Arg292Trp Conflicting classifications of pathogenicity ★ ⚠ 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-arg292gln (accessed [today's date]).

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