Is MYO7A p.Cys1201Ser (c.3602G>C) pathogenic?

MYO7A p.Cys1201Ser (c.3602G>C) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-14). AlphaMissense: likely pathogenic (0.9127); Rare (popmax 0.323%, eas); Associated with Usher syndrome type 1.

What condition is associated with MYO7A p.Cys1201Ser (c.3602G>C)?

MYO7A p.Cys1201Ser (c.3602G>C) is associated with Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2, autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.Cys1201Ser (c.3602G>C) in the general population?

MYO7A p.Cys1201Ser (c.3602G>C) is rare (popmax 0.323%, 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.Cys1201Ser (c.3602G>C)?

AlphaMissense predicts likely pathogenic (score 0.9127) — an in-silico prediction, not a clinical call.

MYO7A p.Cys1201Ser

c.3602G>C · rs117966637 · VCV43215

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.9127 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.323%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.9127	likely pathogenic
REVEL	0.853	moderately pathogenic-leaning
SaProt	LLR -7.08	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	26.4	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 0.323% East Asian · 145/44,868 alleles

Filtering AF 0.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.264%

Overall 0.00954% 154/1,613,886 alleles · rare exomes 125/1,461,610 · genomes 29/152,276 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.323%	309
Remaining individualsnot grpmax-eligible	0.0128%	7,811
South Asian	0.0011%	91,074

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.Cys1201Ser
Coding: c.3602G>C
MANE Select: NM_000260
dbSNP: rs117966637
Type: single nucleotide variant
Location: chr11:77189442 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1201: the myth4 1 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 autosomal dominant nonsyndromic hearing loss 11

For Usher syndrome (Orphanet):

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

Similar variants

MYO7A p.Cys1201Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A p.Cys1201fs 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-cys1201ser (accessed [today's date]).

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