Is ANO5 p.Phe565= (c.1695T>C) pathogenic?

ANO5 p.Phe565= (c.1695T>C) is classified Likely benign in ANO5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-21). Very rare (popmax 0.00267%, afr); Associated with gnathodiaphyseal dysplasia.

What condition is associated with ANO5 p.Phe565= (c.1695T>C)?

ANO5 p.Phe565= (c.1695T>C) is associated with gnathodiaphyseal dysplasia, autosomal recessive limb-girdle muscular dystrophy type 2L (ClinVar).

How common is ANO5 p.Phe565= (c.1695T>C) in the general population?

ANO5 p.Phe565= (c.1695T>C) is very rare (popmax 0.00267%, afr) (gnomAD).

ANO5 p.Phe565=

c.1695T>C · rs142009189 · VCV1596869

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 1.2	GERP -1.1, phastCons 1
Overall
CADD	16.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,936 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,613,900 alleles · very rare exomes 2/1,461,696 · genomes 1/152,204 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,468
East Asian	0.00223%	44,852

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.Phe565=
Coding: c.1695T>C
MANE Select: NM_213599
dbSNP: rs142009189
Type: single nucleotide variant
Location: chr11:22262193 (GRCh38)
Gene constraint: LOEUF 1.034 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.22
Residue 565: 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.Phe565fs 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-phe565 (accessed [today's date]).

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