Is ANO5 p.Ser515= (c.1545A>G) pathogenic?

ANO5 p.Ser515= (c.1545A>G) is classified Benign/Likely benign in ANO5 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-01-27). Low-frequency (popmax 2.08%, afr); Associated with autosomal recessive limb-girdle muscular dystrophy type 2L.

What condition is associated with ANO5 p.Ser515= (c.1545A>G)?

ANO5 p.Ser515= (c.1545A>G) is associated with autosomal recessive limb-girdle muscular dystrophy type 2L, gnathodiaphyseal dysplasia, Miyoshi muscular dystrophy 3 (ClinVar).

How common is ANO5 p.Ser515= (c.1545A>G) in the general population?

ANO5 p.Ser515= (c.1545A>G) is low-frequency (popmax 2.08%, afr) (gnomAD).

ANO5 p.Ser515=

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.1545A>G · rs35843353 · VCV140550

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.08%, afr)

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 0.057	GERP -5.2, phastCons 0.14
Overall
CADD	6.791	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.08% African / African-American · 1,559/75,026 alleles

Filtering AF 1.99% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.96%

Overall 0.111% 1,787/1,614,042 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.08%	48
Remaining individualsnot grpmax-eligible	0.17%	590
Admixed American	0.152%	660
Middle Eastern	0.115%	866
South Asian	0.00329%	30,357
European (non-Finnish)	0.00178%	56,189

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.Ser515=
Coding: c.1545A>G
MANE Select: NM_213599
dbSNP: rs35843353
Type: single nucleotide variant
Location: chr11:22259656 (GRCh38)
Gene constraint: LOEUF 1.034 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.22
Residue 515: a UniProt-annotated variant site (in lgmdr12)

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 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.Ser515Ter Pathogenic ★ same residue
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

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-ser515 (accessed [today's date]).

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