Is MYO7A p.Tyr108= (c.324C>T) pathogenic?

MYO7A p.Tyr108= (c.324C>T) is classified Benign in MYO7A (ClinVar, Expert panel, 8 submitters; last evaluated 2018-09-28). Rare (popmax 0.817%, eas); Associated with nonsyndromic genetic hearing loss.

What condition is associated with MYO7A p.Tyr108= (c.324C>T)?

MYO7A p.Tyr108= (c.324C>T) is associated with nonsyndromic genetic hearing loss, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Tyr108= (c.324C>T) in the general population?

MYO7A p.Tyr108= (c.324C>T) is rare (popmax 0.817%, eas) (gnomAD).

How is Rare non-syndromic genetic deafness inherited?

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

MYO7A p.Tyr108=

c.324C>T · rs116892396 · VCV43201

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.817%, eas)

Conditions

nonsyndromic genetic hearing loss

ClinGen expert panel — Hearing Loss VCEP

Benign for nonsyndromic genetic deafness. Applied ACMG criteria (verbatim):

BA1

Curation rationale (ClinGen, verbatim)

The filtering allele frequency of the p.Tyr108= variant in the MYO7A gene is 1.45% (300/18658) of East Asian chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal dominant hearing loss variants (BA1).

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.76 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.83	GERP -0.37, phastCons 1
Overall
CADD	8.369	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.817% East Asian · 366/44,798 alleles

Filtering AF 0.748% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.721%

Overall 0.0243% 391/1,611,436 alleles · rare exomes 331/1,459,070 · genomes 60/152,366 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.817%	122
Remaining individualsnot grpmax-eligible	0.0353%	2,837
South Asian	0.00221%	45,214
Admixed American	0.00167%	59,718

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.Tyr108=
Coding: c.324C>T
MANE Select: NM_000260
dbSNP: rs116892396
Type: single nucleotide variant
Location: chr11:77155945 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 108: the myosin motor domain

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

Disease context

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

Also linked: Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 2 autosomal dominant nonsyndromic hearing loss 11 Usher syndrome type 1B

For Rare non-syndromic genetic deafness (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

MYO7A p.Tyr108Ter 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
MYO7A p.Glu968Asp 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-tyr108 (accessed [today's date]).

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