Is MYO7A p.Gly2177fs (c.6528_6529del) pathogenic?

MYO7A p.Gly2177fs (c.65286529del) is classified Likely pathogenic in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2017-06-13). Very rare (popmax 0.0011%, sas); Associated with MYO7A-related disorder.

What condition is associated with MYO7A p.Gly2177fs (c.6528_6529del)?

MYO7A p.Gly2177fs (c.6528_6529del) is associated with MYO7A-related disorder (ClinVar).

How common is MYO7A p.Gly2177fs (c.6528_6529del) in the general population?

MYO7A p.Gly2177fs (c.6528_6529del) is very rare (popmax 0.0011%, sas) (gnomAD).

MYO7A p.Gly2177fs

c.6528_6529del · VCV4913321

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (48 of 49, 33 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.1	GERP 0.82, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,086 alleles

Overall 6.2e-05% 1/1,614,054 alleles · very rare exomes 1/1,461,696 · genomes 0/152,358 · 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.Gly2177fs
Coding: c.6528_6529del
MANE Select: NM_000260
Type: Microsatellite
Location: chr11:77213946 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 2177: the ferm 2 domain

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

Disease context

MYO7A-related disorder

Similar variants

MYO7A p.Asn1182fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Phe1963del Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Val1501fs Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Gly2177Arg Uncertain significance ★★ ⚠ same residue
MYO7A p.Glu2095_Ala2096insGlu Likely pathogenic ★ same condition
MYO7A p.Gly2177= Likely benign ★ same residue
MYO7A c.133-2A>G Pathogenic ★★ same condition
MYO7A c.1344-2A>G 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-gly2177fs (accessed [today's date]).

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