Is MYO7A p.Cys2182= (c.6546C>T) pathogenic?

MYO7A p.Cys2182= (c.6546C>T) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0346%, afr); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Cys2182= (c.6546C>T)?

MYO7A p.Cys2182= (c.6546C>T) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Cys2182= (c.6546C>T) in the general population?

MYO7A p.Cys2182= (c.6546C>T) is ultra-rare (popmax 0.0346%, afr) (gnomAD).

MYO7A p.Cys2182=

c.6546C>T · rs185748200 · VCV708108

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0346%, afr)

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.30	donor gain · deltas
Constraint at this position
Conservation	phyloP -1.1	GERP -3.8, phastCons 0.004
Overall
CADD	12.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0346% African / African-American · 26/75,070 alleles

Filtering AF 0.0242% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0215%

Overall 0.0212% 342/1,614,050 alleles · ultra-rare exomes 302/1,461,680 · genomes 40/152,370 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0346%	2,887
Remaining individualsnot grpmax-eligible	0.0256%	3,906
European (non-Finnish)	0.0247%	4,041
East Asian	0.00891%	11,222
South Asian	0.00439%	22,771

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.Cys2182=
Coding: c.6546C>T
MANE Select: NM_000260
dbSNP: rs185748200
Type: single nucleotide variant
Location: chr11:77213967 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 2182: the ferm 2 domain; a β-strand

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.Cys2182Ter Pathogenic ★ same residue
MYO7A p.Cys2182Ser 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-cys2182 (accessed [today's date]).

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