Is ANO5 p.Arg109= (c.327A>G) pathogenic?

ANO5 p.Arg109= (c.327A>G) is classified Likely benign in ANO5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-15). Very rare (popmax 0.0017%, nfe); Associated with gnathodiaphyseal dysplasia.

What condition is associated with ANO5 p.Arg109= (c.327A>G)?

ANO5 p.Arg109= (c.327A>G) is associated with gnathodiaphyseal dysplasia, autosomal recessive limb-girdle muscular dystrophy type 2L (ClinVar).

How common is ANO5 p.Arg109= (c.327A>G) in the general population?

ANO5 p.Arg109= (c.327A>G) is very rare (popmax 0.0017%, nfe) (gnomAD).

ANO5 p.Arg109=

c.327A>G · VCV3753345

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0017%, nfe)

Conditions

gnathodiaphyseal dysplasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.3	GERP -1.2, phastCons 0.85
Overall
CADD	10.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0017% European (non-Finnish) · 20/1,175,866 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000903%

Overall 0.00124% 20/1,609,008 alleles · very rare exomes 20/1,456,728 · genomes 0/152,280 · joint denominator

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.Arg109=
Coding: c.327A>G
MANE Select: NM_213599
Type: single nucleotide variant
Location: chr11:22226016 (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

gnathodiaphyseal dysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2L

Similar variants

ANO5 p.Arg109Lys 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-arg109 (accessed [today's date]).

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