Is MYO7A p.Val1815fs (c.5441_5442dup) pathogenic?

MYO7A p.Val1815fs (c.54415442dup) is classified Pathogenic in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-01). Very rare (popmax 6.31e-05%); Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Val1815fs (c.5441_5442dup)?

MYO7A p.Val1815fs (c.5441_5442dup) is associated with autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Val1815fs (c.5441_5442dup) in the general population?

MYO7A p.Val1815fs (c.5441_5442dup) is very rare (popmax 6.31e-05%) (gnomAD).

MYO7A p.Val1815fs

c.5441_5442dup · rs2497683918 · VCV3239682

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.31e-05%)

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 39 of 49
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.88	GERP -0.68, phastCons 0.58

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.31e-05%

Overall 6.31e-05% 1/1,585,168 alleles · very rare exomes 1/1,432,834 · genomes 0/152,334 · 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.Val1815fs
Coding: c.5441_5442dup
MANE Select: NM_000260
dbSNP: rs2497683918
Type: Microsatellite
Location: chr11:77204187 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1815: the myth4 2 domain; an α-helix

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.Leu1116fs 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-val1815fs (accessed [today's date]).

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