Is ANO5 p.Arg654= (c.1962A>G) pathogenic?

ANO5 p.Arg654= (c.1962A>G) is classified Likely benign in ANO5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-01). Absent from gnomAD v4.1; Associated with gnathodiaphyseal dysplasia.

What condition is associated with ANO5 p.Arg654= (c.1962A>G)?

ANO5 p.Arg654= (c.1962A>G) is associated with gnathodiaphyseal dysplasia, autosomal recessive limb-girdle muscular dystrophy type 2L (ClinVar).

How common is ANO5 p.Arg654= (c.1962A>G) in the general population?

ANO5 p.Arg654= (c.1962A>G) is absent from gnomAD v4.1 (gnomAD).

ANO5 p.Arg654=

c.1962A>G · rs1057521970 · VCV384498

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

gnathodiaphyseal dysplasia

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 0.3	GERP -5.2, phastCons 0.75
Overall
CADD	6.682	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANO5
Protein: p.Arg654=
Coding: c.1962A>G
MANE Select: NM_213599
dbSNP: rs1057521970
Type: single nucleotide variant
Location: chr11:22270375 (GRCh38)
Gene constraint: LOEUF 1.034 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.22
Residue 654: a UniProt-annotated variant site (in lgmdr12); a UniProt-annotated variant site (in lgmdr12; uncertain significance)

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.Arg654Ter Pathogenic/Likely pathogenic ★★ same residue
ANO5 p.Arg654Gln Uncertain significance ★ ⚠ same residue
ANO5 p.Arg654Leu 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

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-arg654 (accessed [today's date]).

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