Is MYO7A p.Cys1554fs (c.4659_4660del) pathogenic?

MYO7A p.Cys1554fs (c.46594660del) is classified Likely pathogenic in MYO7A (ClinVar, Single submitter, 2 submitters; last evaluated 2022-11-06). Very rare (popmax 8.49e-05%, nfe); Associated with MYO7A-related disorder.

What condition is associated with MYO7A p.Cys1554fs (c.4659_4660del)?

MYO7A p.Cys1554fs (c.4659_4660del) is associated with MYO7A-related disorder, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Cys1554fs (c.4659_4660del) in the general population?

MYO7A p.Cys1554fs (c.4659_4660del) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

MYO7A p.Cys1554fs

c.4659_4660del · rs1555100315 · VCV558331

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Conditions

MYO7A-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 35 of 49
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.1	GERP 0.38, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,178,066 alleles

Overall 6.22e-05% 1/1,608,584 alleles · very rare exomes 1/1,456,266 · genomes 0/152,318 · 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.Cys1554fs
Coding: c.4659_4660del
MANE Select: NM_000260
dbSNP: rs1555100315
Type: Deletion
Location: chr11:77199625 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1554: the ferm 1 domain

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

Disease context

MYO7A-related disorder

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

Similar variants

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
MYO7A p.Asp1613fs 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-cys1554fs (accessed [today's date]).

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