Is ANO5 p.Phe82fs (c.246del) pathogenic?

ANO5 p.Phe82fs (c.246del) is classified Pathogenic in ANO5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-24). Very rare (popmax 0.00133%, afr); Associated with gnathodiaphyseal dysplasia.

What condition is associated with ANO5 p.Phe82fs (c.246del)?

ANO5 p.Phe82fs (c.246del) is associated with gnathodiaphyseal dysplasia, autosomal recessive limb-girdle muscular dystrophy type 2L (ClinVar).

How common is ANO5 p.Phe82fs (c.246del) in the general population?

ANO5 p.Phe82fs (c.246del) is very rare (popmax 0.00133%, afr) (gnomAD).

ANO5 p.Phe82fs

c.246del · rs1852636503 · VCV2947083

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

gnathodiaphyseal dysplasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.2	GERP 2.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,956 alleles

Overall 6.2e-05% 1/1,612,050 alleles · very rare exomes 1/1,459,900 · genomes 0/152,150 · 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.Phe82fs
Coding: c.246del
MANE Select: NM_213599
dbSNP: rs1852636503
Type: Deletion
Location: chr11:22221159 (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.Phe82= Likely benign ★ same residue
ANO5 p.Lys102fs Pathogenic ★★★ same condition
ANO5 p.Phe835del Likely pathogenic ★★★ same condition
ANO5 c.139-1del Uncertain significance ★★★ same condition
ANO5 c.2236-21_2236-17del Likely benign ★★★ same condition
ANO5 c.364-8del Benign ★★★ same condition
ANO5 c.1631-12_1631-2del Pathogenic/Likely pathogenic ★★ same condition
ANO5 p.Ala144fs 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-phe82fs (accessed [today's date]).

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