Is ANO5 p.Lys92= (c.276A>G) pathogenic?

ANO5 p.Lys92= (c.276A>G) is classified Conflicting classifications of pathogenicity in ANO5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-18). Very rare (popmax 0.00782%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy type 2L.

How common is ANO5 p.Lys92= (c.276A>G) in the general population?

ANO5 p.Lys92= (c.276A>G) is very rare (popmax 0.00782%, nfe) (gnomAD).

ANO5 p.Lys92=

Q: What condition is associated with ANO5 p.Lys92= (c.276A>G)?

ANO5 p.Lys92= (c.276A>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.276A>G · rs201678262 · VCV285124

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00782%, 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 3.4	GERP 1.1, phastCons 1
Overall
CADD	4.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00782% European (non-Finnish) · 92/1,176,626 alleles

Filtering AF 0.00649% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00602%

Overall 0.0059% 95/1,609,458 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00782%	12,789
Remaining individualsnot grpmax-eligible	0.00482%	20,751

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.Lys92=
Coding: c.276A>G
MANE Select: NM_213599
dbSNP: rs201678262
Type: single nucleotide variant
Location: chr11:22221192 (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 p.Lys92Glu Uncertain significance ★ ⚠ 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-lys92 (accessed [today's date]).

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