Is MYO7A p.Arg830Cys (c.2488C>T) pathogenic?

MYO7A p.Arg830Cys (c.2488C>T) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-09-15). AlphaMissense: ambiguous (0.4445); Very rare (popmax 0.00244%, eas); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Arg830Cys (c.2488C>T)?

MYO7A p.Arg830Cys (c.2488C>T) is associated with Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2, Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Arg830Cys (c.2488C>T) in the general population?

MYO7A p.Arg830Cys (c.2488C>T) is very rare (popmax 0.00244%, eas) (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.Arg830Cys (c.2488C>T)?

AlphaMissense predicts ambiguous (score 0.4445) — an in-silico prediction, not a clinical call.

MYO7A p.Arg830Cys

c.2488C>T · rs797044493 · VCV164681

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.4445 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00244%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Usher syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.4445	ambiguous
REVEL	0.797	moderately pathogenic-leaning
SaProt	LLR -10.51	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	Δ0.26	donor loss, 4 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	33.0	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 0.00244% East Asian · 1/40,914 alleles

Filtering AF 0.0015% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00126%

Overall 0.00182% 28/1,542,010 alleles · very rare exomes 28/1,389,642 · genomes 0/152,368 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00244%	40,914
European (non-Finnish)	0.00218%	45,872
Admixed American	0.00196%	51,012
South Asian	0.00119%	84,012

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.Arg830Cys
Coding: c.2488C>T
MANE Select: NM_000260
dbSNP: rs797044493
Type: single nucleotide variant
Location: chr11:77179855 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 830: the iq 4 domain

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: autosomal recessive nonsyndromic hearing loss 2 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.Arg830His Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Arg830Leu Uncertain significance ★ ⚠ same residue
MYO7A p.Arg830Ser 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-arg830cys (accessed [today's date]).

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