Is MYO7A p.Leu1116fs (c.3346_3347del) pathogenic?

MYO7A p.Leu1116fs (c.33463347del) is classified Pathogenic in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). Very rare (popmax 0.00244%, eas); Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Leu1116fs (c.3346_3347del)?

MYO7A p.Leu1116fs (c.3346_3347del) is associated with autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Leu1116fs (c.3346_3347del) in the general population?

MYO7A p.Leu1116fs (c.3346_3347del) is very rare (popmax 0.00244%, eas) (gnomAD).

MYO7A p.Leu1116fs

c.3346_3347del · VCV3601470

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00244%, eas)

Conditions

autosomal recessive nonsyndromic hearing loss 2

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 26 of 49
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00244% East Asian · 1/40,990 alleles

Overall 6.44e-05% 1/1,552,170 alleles · very rare exomes 0/1,400,082 · genomes 1/152,088 · 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.Leu1116fs
Coding: c.3346_3347del
MANE Select: NM_000260
Type: Microsatellite
Location: chr11:77183126 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1116: 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

Similar variants

MYO7A p.Glu1716del Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Phe1963del Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ser423fs Likely pathogenic ★★ same condition
MYO7A p.Trp47fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Val1501fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Arg1448del Uncertain significance ★★ same condition
MYO7A p.Phe1346del Uncertain significance ★★ same condition
MYO7A p.Val1815fs 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-leu1116fs (accessed [today's date]).

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