Is ANO5 p.Asp89= (c.267T>C) pathogenic?

ANO5 p.Asp89= (c.267T>C) is classified Benign in ANO5 (ClinVar, Multiple submitters, 20 submitters; last evaluated 2026-02-04). Common (popmax 93.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with gnathodiaphyseal dysplasia.

What condition is associated with ANO5 p.Asp89= (c.267T>C)?

ANO5 p.Asp89= (c.267T>C) is associated with gnathodiaphyseal dysplasia, autosomal recessive limb-girdle muscular dystrophy type 2L, Miyoshi muscular dystrophy 3 (ClinVar).

ANO5 p.Asp89=

Q: How common is ANO5 p.Asp89= (c.267T>C) in the general population?

ANO5 p.Asp89= (c.267T>C) is common (popmax 93.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.267T>C · rs4312063 · VCV96681

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 20 submitters

gnomAD v4.1

Common

common (popmax 93.3%, afr) — too common for a highly-penetrant pathogenic allele

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 -5	GERP -4.4
Overall
CADD	0.594	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 93.3% African / African-American · 69,830/74,872 alleles

Filtering AF 92.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 92.4%

Overall 80% 1,287,797/1,610,396 alleles · common exomes 1,162,290/1,458,460 · genomes 125,507/151,936 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	93.3%	1
Amishnot grpmax-eligible	87.7%	1
Middle Eastern	81.7%	1
Finnishnot grpmax-eligible	81.3%	1
European (non-Finnish)	81%	1
South Asian	80.3%	1
Remaining individualsnot grpmax-eligible	79.5%	1
Ashkenazi Jewishnot grpmax-eligible	75.2%	1
Admixed American	64.2%	2
East Asian	53.1%	2

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.Asp89=
Coding: c.267T>C
MANE Select: NM_213599
dbSNP: rs4312063
Type: single nucleotide variant
Location: chr11:22221183 (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 Miyoshi muscular dystrophy 3

Similar variants

ANO5 p.Asp89Val 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-asp89 (accessed [today's date]).

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