Is ANO5 p.Phe593fs (c.1777_1780del) pathogenic?

ANO5 p.Phe593fs (c.17771780del) is classified Likely pathogenic in ANO5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-02). Associated with autosomal recessive limb-girdle muscular dystrophy type 2L.

ANO5 p.Phe593fs

Q: What condition is associated with ANO5 p.Phe593fs (c.1777_1780del)?

ANO5 p.Phe593fs (c.1777_1780del) is associated with autosomal recessive limb-girdle muscular dystrophy type 2L, Miyoshi muscular dystrophy 3 (ClinVar).

Q: How is Anoctamin-5-related limb-girdle muscular dystrophy R12 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1777_1780del · VCV3896778

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2L

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 16 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.8	GERP -5.5

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

Variant & gene context

Gene: ANO5
Protein: p.Phe593fs
Coding: c.1777_1780del
MANE Select: NM_213599
Type: Microsatellite
Location: chr11:22262269 (GRCh38)
Gene constraint: LOEUF 1.034 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.22
Residue 593: a UniProt-annotated variant site (in lgmdr12); a UniProt-annotated variant site (in lgmdr12; uncertain significance)

Full ANO5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2L — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Miyoshi muscular dystrophy 3

For Anoctamin-5-related limb-girdle muscular dystrophy R12 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

Similar variants

ANO5 p.Glu36fs Pathogenic ★★★ same condition
ANO5 p.Gln771fs Pathogenic ★★ same condition
ANO5 p.Phe208del Uncertain significance ★★ same condition
ANO5 p.Ter914IleextTer? Uncertain significance ★★ same condition
ANO5 p.Trp639del Uncertain significance ★★ same condition
ANO5 c.2414+5TTTG[3] Likely benign ★★ same condition
ANO5 c.41-15_41-12del Likely benign ★★ same condition
ANO5 p.Glu95fs 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/ano5-p-phe593fs (accessed [today's date]).

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