Is ANO5 p.Asp93= (c.279C>T) pathogenic?

ANO5 p.Asp93= (c.279C>T) is classified Conflicting classifications of pathogenicity in ANO5 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-23). Ultra-rare (popmax 0.077%, amr); Associated with gnathodiaphyseal dysplasia.

What condition is associated with ANO5 p.Asp93= (c.279C>T)?

ANO5 p.Asp93= (c.279C>T) is associated with gnathodiaphyseal dysplasia, autosomal recessive limb-girdle muscular dystrophy type 2L (ClinVar).

How common is ANO5 p.Asp93= (c.279C>T) in the general population?

ANO5 p.Asp93= (c.279C>T) is ultra-rare (popmax 0.077%, amr) (gnomAD).

ANO5 p.Asp93=

c.279C>T · rs148516756 · VCV281458

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.077%, amr)

Conditions

gnathodiaphyseal dysplasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.7	GERP -4.4
Overall
CADD	0.854	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.077% Admixed American · 46/59,734 alleles

Filtering AF 0.0593% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.053%

Overall 0.00964% 155/1,608,672 alleles · ultra-rare exomes 131/1,456,732 · genomes 24/151,940 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.149%	670
Admixed Americangrpmax	0.077%	1,299
Remaining individualsnot grpmax-eligible	0.0209%	4,789
South Asian	0.0132%	7,580
European (non-Finnish)	0.00323%	30,946
Finnishnot grpmax-eligible	0.00157%	63,856
African / African-American	0.00134%	74,792

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp93=
Coding: c.279C>T
MANE Select: NM_213599
dbSNP: rs148516756
Type: single nucleotide variant
Location: chr11:22221195 (GRCh38)
Gene constraint: LOEUF 1.034 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.22
Residue 93: 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.Asp93Gly Uncertain significance ★★ ⚠ same residue
ANO5 p.Asp93Asn Uncertain significance ★ ⚠ same residue
ANO5 p.Asp93Glu 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-asp93 (accessed [today's date]).

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