Is MYO7A p.Cys652= (c.1956C>T) pathogenic?

MYO7A p.Cys652= (c.1956C>T) is classified Likely benign in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-11). Very rare (popmax 0.00268%, afr); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Cys652= (c.1956C>T)?

MYO7A p.Cys652= (c.1956C>T) is associated with Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Cys652= (c.1956C>T) in the general population?

MYO7A p.Cys652= (c.1956C>T) is very rare (popmax 0.00268%, afr) (gnomAD).

How is Usher syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MYO7A p.Cys652=

c.1956C>T · rs367693437 · VCV43166

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

Conditions

Usher syndrome type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.2	GERP -3.5
Overall
CADD	3.316	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00268% African / African-American · 2/74,676 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000562% 9/1,601,000 alleles · very rare exomes 7/1,448,776 · genomes 2/152,224 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00268%	37,338
South Asian	0.00113%	88,854
European (non-Finnish)	0.000511%	195,745

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.Cys652=
Coding: c.1956C>T
MANE Select: NM_000260
dbSNP: rs367693437
Type: single nucleotide variant
Location: chr11:77174776 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 652: the myosin motor domain; a UniProt-annotated variant site (in dfnb2)

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

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

MYO7A p.Cys652Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Cys652Arg Pathogenic/Likely pathogenic ★★ 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-cys652 (accessed [today's date]).

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