Is MYO7A p.Arg834Cys (c.2500C>T) pathogenic?

MYO7A p.Arg834Cys (c.2500C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-05-27). AlphaMissense: likely benign (0.1376); Very rare (popmax 0.00981%, amr); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Arg834Cys (c.2500C>T)?

MYO7A p.Arg834Cys (c.2500C>T) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Arg834Cys (c.2500C>T) in the general population?

MYO7A p.Arg834Cys (c.2500C>T) is very rare (popmax 0.00981%, amr) (gnomAD).

What do computational predictors say about MYO7A p.Arg834Cys (c.2500C>T)?

AlphaMissense predicts likely benign (score 0.1376) — an in-silico prediction, not a clinical call.

MYO7A p.Arg834Cys

c.2500C>T · rs781869469 · VCV851143

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1376 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00981%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
AlphaMissense	0.1376	likely benign
REVEL	0.563	indeterminate
SaProt	LLR -10.31	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.5	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 0.00981% Admixed American · 5/50,986 alleles

Filtering AF 0.00382% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00248%

Overall 0.00169% 26/1,541,190 alleles · very rare exomes 24/1,388,934 · genomes 2/152,256 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00981%	10,197
Remaining individualsnot grpmax-eligible	0.00167%	59,928
European (non-Finnish)	0.00166%	60,357
African / African-American	0.00137%	73,024

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.Arg834Cys
Coding: c.2500C>T
MANE Select: NM_000260
dbSNP: rs781869469
Type: single nucleotide variant
Location: chr11:77179867 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 834: the iq 4 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.Arg834His Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg834Leu 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-arg834cys (accessed [today's date]).

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