Is MYO7A c.*363A>C pathogenic?

MYO7A c.363A>C is classified Benign/Likely benign in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-05-15). Common (popmax 5.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autosomal dominant nonsyndromic hearing loss 11.

What condition is associated with MYO7A c.*363A>C?

MYO7A c.*363A>C is associated with autosomal dominant nonsyndromic hearing loss 11, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

MYO7A c.*363A>C

Q: How common is MYO7A c.*363A>C in the general population?

MYO7A c.*363A>C is common (popmax 5.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs115872143 · VCV306208

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.9%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

autosomal dominant nonsyndromic hearing loss 11

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 -2.2	GERP -1.5
Non-coding constraint	Z -0.16	1 kb window · o/e 1.01 · regional · uncalibrated
Overall
CADD	1.971	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.9% African / African-American · 2,662/45,088 alleles

Filtering AF 5.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.64%

Overall 1.17% 2,897/247,134 alleles · common exomes 245/94,820 · genomes 2,652/152,314 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.9%	17
Admixed American	0.743%	135
Remaining individualsnot grpmax-eligible	0.674%	148
Middle Eastern	0.398%	251
European (non-Finnish)	0.022%	4,551
South Asian	0.0162%	6,161

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
Coding: c.*363A>C
MANE Select: NM_000260
dbSNP: rs115872143
Type: single nucleotide variant
Location: chr11:77215059 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB

Full MYO7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant nonsyndromic hearing loss 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 2

Similar variants

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
MYO7A p.Glu968Asp Likely pathogenic ★★★ ⚠ same condition
MYO7A p.Gly2187Asp 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-c-star-363a-c (accessed [today's date]).

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