Is MYO7A p.Pro1244fs (c.3728dup) pathogenic?

MYO7A p.Pro1244fs (c.3728dup) is classified Pathogenic/Likely pathogenic in MYO7A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-10-04). Very rare (popmax 0.00135%, afr); Associated with Rare genetic deafness.

What condition is associated with MYO7A p.Pro1244fs (c.3728dup)?

MYO7A p.Pro1244fs (c.3728dup) is associated with Rare genetic deafness, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Pro1244fs (c.3728dup) in the general population?

MYO7A p.Pro1244fs (c.3728dup) is very rare (popmax 0.00135%, afr) (gnomAD).

MYO7A p.Pro1244fs

c.3728dup · rs397516304 · VCV43219

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Conditions

Rare genetic deafness

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 29 of 49
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP -1.8, 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 0.00135% African / African-American · 1/74,064 alleles

Overall 6.36e-05% 1/1,573,058 alleles · very rare exomes 0/1,420,796 · genomes 1/152,262 · 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.Pro1244fs
Coding: c.3728dup
MANE Select: NM_000260
dbSNP: rs397516304
Type: Duplication
Location: chr11:77190115 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1244: the myth4 1 domain

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

Disease context

Rare genetic deafness — 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 Usher syndrome type 1B

Similar variants

MYO7A p.Pro1244Arg Uncertain significance ★★ ⚠ same residue
MYO7A p.Asp365fs Pathogenic ★★ same condition
MYO7A p.Glu1830fs Likely pathogenic ★★ same condition
MYO7A p.Gly1842fs Pathogenic ★★ same condition
MYO7A p.His133fs Pathogenic ★★ same condition
MYO7A p.Ile454fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ile94fs Likely pathogenic ★★ same condition
MYO7A p.Leu1046fs 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-pro1244fs (accessed [today's date]).

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