Is ANO5 p.Lys232= (c.696G>A) pathogenic?

ANO5 p.Lys232= (c.696G>A) is classified Uncertain significance in ANO5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-20). Very rare (popmax 0.004%, afr); Associated with autosomal recessive limb-girdle muscular dystrophy type 2L.

How common is ANO5 p.Lys232= (c.696G>A) in the general population?

ANO5 p.Lys232= (c.696G>A) is very rare (popmax 0.004%, afr) (gnomAD).

ANO5 p.Lys232=

Q: What condition is associated with ANO5 p.Lys232= (c.696G>A)?

ANO5 p.Lys232= (c.696G>A) 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.696G>A · rs773606619 · VCV290675

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2L

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	acceptor loss, 47 bp away · masked 0 · deltas
Pangolin	Δ0.30	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.5	GERP -0.02, phastCons 1
Overall
CADD	4.845	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,910 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00167% 27/1,613,338 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,970
European (non-Finnish)	0.00195%	51,288
Remaining individualsnot grpmax-eligible	0.0016%	62,444

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.Lys232=
Coding: c.696G>A
MANE Select: NM_213599
dbSNP: rs773606619
Type: single nucleotide variant
Location: chr11:22236210 (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-lys232 (accessed [today's date]).

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