Is ANO5 p.Glu43= (c.129A>G) pathogenic?

ANO5 p.Glu43= (c.129A>G) is classified Likely benign in ANO5 (ClinVar, Single submitter, 3 submitters; last evaluated 2025-11-24). Ultra-rare (popmax 0.0126%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy type 2L.

How common is ANO5 p.Glu43= (c.129A>G) in the general population?

ANO5 p.Glu43= (c.129A>G) is ultra-rare (popmax 0.0126%, nfe) (gnomAD).

ANO5 p.Glu43=

Q: What condition is associated with ANO5 p.Glu43= (c.129A>G)?

ANO5 p.Glu43= (c.129A>G) is associated with autosomal recessive limb-girdle muscular dystrophy type 2L, gnathodiaphyseal dysplasia (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.129A>G · rs149627067 · VCV1100663

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0126%, nfe)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -2.9, phastCons 0.87
Overall
CADD	1.272	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0126% European (non-Finnish) · 148/1,178,682 alleles

Filtering AF 0.0109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0103%

Overall 0.0093% 150/1,612,130 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0126%	7,964
Remaining individualsnot grpmax-eligible	0.0016%	62,364
African / African-American	0.00134%	74,828

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: ANO5
Protein: p.Glu43=
Coding: c.129A>G
MANE Select: NM_213599
dbSNP: rs149627067
Type: single nucleotide variant
Location: chr11:22211305 (GRCh38)
Gene constraint: LOEUF 1.034 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.22

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: gnathodiaphyseal dysplasia

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

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

Similar variants

ANO5 c.1898+1G>A Pathogenic ★★★ same condition
ANO5 c.41-1G>A Pathogenic ★★★ same condition
ANO5 p.Ala432Gly Pathogenic ★★★ ⚠ same condition
ANO5 p.Arg484Cys Likely pathogenic ★★★ same condition
ANO5 p.Arg50Ter Pathogenic ★★★ same condition
ANO5 p.Arg58Trp Pathogenic ★★★ ⚠ same condition
ANO5 p.Arg758Cys Pathogenic ★★★ same condition
ANO5 p.Asp81Gly 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-glu43 (accessed [today's date]).

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