Is GAA p.Cys82= (c.246C>T) pathogenic?

GAA p.Cys82= (c.246C>T) is classified Likely benign in GAA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-05). Ultra-rare (popmax 0.0164%, mid); Associated with glycogen storage disease II.

What condition is associated with GAA p.Cys82= (c.246C>T)?

GAA p.Cys82= (c.246C>T) is associated with glycogen storage disease II (ClinVar).

How common is GAA p.Cys82= (c.246C>T) in the general population?

GAA p.Cys82= (c.246C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

GAA p.Cys82=

Q: How is Glycogen storage disease due to acid maltase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.246C>T · rs749584846 · VCV753262

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

glycogen storage disease II

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 -6.6	GERP -2.7
Overall
CADD	0.766	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00727% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00174% 28/1,612,268 alleles · ultra-rare exomes 22/1,460,052 · genomes 6/152,216 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
East Asian	0.0156%	6,404
African / African-American	0.00934%	10,703
South Asian	0.00769%	13,005
Remaining individualsnot grpmax-eligible	0.0032%	31,218
European (non-Finnish)	0.000339%	294,957

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: GAA
Protein: p.Cys82=
Coding: c.246C>T
MANE Select: NM_000152
dbSNP: rs749584846
Type: single nucleotide variant
Location: chr17:80104832 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.32 · 19 PDB
Residue 82: an α-helix; a disulfide bond; the p-type domain; the 'disordered' region

Full GAA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

glycogen storage disease II — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycogen storage disease due to acid maltase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

GAA p.Cys82Ter Pathogenic ★★★ same residue
GAA p.Cys82Arg Uncertain significance ★ ⚠ same residue
GAA p.Cys82Gly Uncertain significance ★ ⚠ same residue
GAA c.1076-1G>C Pathogenic ★★★ same condition
GAA c.1076-22T>G Pathogenic ★★★ same condition
GAA c.1194+5G>A Likely pathogenic ★★★ same condition
GAA c.1326+1G>A Pathogenic ★★★ same condition
GAA c.1327-2A>G 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/gaa-p-cys82 (accessed [today's date]).

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