Is MYO7A p.Tyr1017del (c.3049_3051del) pathogenic?

MYO7A p.Tyr1017del (c.30493051del) is classified Uncertain significance in MYO7A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-05-02). Very rare (popmax 0.000339%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Tyr1017del (c.3049_3051del)?

MYO7A p.Tyr1017del (c.3049_3051del) is associated with autosomal recessive nonsyndromic hearing loss 2, Usher syndrome type 1 (ClinVar).

How common is MYO7A p.Tyr1017del (c.3049_3051del) in the general population?

MYO7A p.Tyr1017del (c.3049_3051del) is very rare (popmax 0.000339%, nfe) (gnomAD).

MYO7A p.Tyr1017del

c.3049_3051del · rs1180304045 · VCV558167

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

autosomal recessive nonsyndromic hearing loss 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP 1.8, phastCons 1
Overall
CADD	17.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,856 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,280 alleles · very rare exomes 3/1,461,146 · genomes 1/152,134 · joint denominator

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.Tyr1017del
Coding: c.3049_3051del
MANE Select: NM_000260
dbSNP: rs1180304045
Type: Deletion
Location: chr11:77182094 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1017: the myth4 1 domain

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

Disease context

autosomal recessive nonsyndromic hearing loss 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1

Similar variants

MYO7A p.Tyr1017Ter Pathogenic ★ same residue
MYO7A c.3503+12_3503+33del Benign ★★★ same condition
MYO7A c.2187+2_2187+8del Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.2283-2_2293del Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1277fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala2009fs Pathogenic ★★ same condition
MYO7A p.Ala202fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Asn769fs 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-tyr1017del (accessed [today's date]).

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