Is MYO7A p.Ala2009fs (c.6025del) pathogenic?

MYO7A p.Ala2009fs (c.6025del) is classified Pathogenic in MYO7A (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-03). Very rare (popmax 0.00656%, nfe); Associated with MYO7A-related disorder.

What condition is associated with MYO7A p.Ala2009fs (c.6025del)?

MYO7A p.Ala2009fs (c.6025del) is associated with MYO7A-related disorder, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Ala2009fs (c.6025del) in the general population?

MYO7A p.Ala2009fs (c.6025del) is very rare (popmax 0.00656%, nfe) (gnomAD).

MYO7A p.Ala2009fs

c.6025del · rs397516326 · VCV43313

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00656%, 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 44 of 49
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.2	GERP -0.67, phastCons 1
Overall
CADD	35.0	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 0.00656% European (non-Finnish) · 76/1,159,370 alleles

Filtering AF 0.00537% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0049%

Overall 0.00502% 79/1,573,846 alleles · very rare exomes 74/1,421,616 · genomes 5/152,230 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00656%	15,255
Remaining individualsnot grpmax-eligible	0.00492%	20,333

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.Ala2009fs
Coding: c.6025del
MANE Select: NM_000260
dbSNP: rs397516326
Type: Deletion
Location: chr11:77208776 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 2009: the ferm 2 domain; an α-helix

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 autosomal dominant nonsyndromic hearing loss 11 inherited retinal dystrophy Usher syndrome type 1B

Similar variants

MYO7A p.Ala2009Thr Likely pathogenic ★★ ⚠ same residue
MYO7A p.Ala2009Asp Conflicting classifications of pathogenicity ★ ⚠ 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 c.5471_5480+5del Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1277fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala202fs Pathogenic/Likely 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-ala2009fs (accessed [today's date]).

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