Is GAA p.Cys103= (c.309C>T) pathogenic?

GAA p.Cys103= (c.309C>T) is classified Likely benign in GAA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-25). Very rare (popmax 0.00667%, amr); Associated with glycogen storage disease II.

What condition is associated with GAA p.Cys103= (c.309C>T)?

GAA p.Cys103= (c.309C>T) is associated with glycogen storage disease II (ClinVar).

How common is GAA p.Cys103= (c.309C>T) in the general population?

GAA p.Cys103= (c.309C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

GAA p.Cys103=

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.309C>T · rs373307393 · VCV577338

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Conditions

glycogen storage disease II

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 -7	GERP -2.7
Overall
CADD	0.475	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/59,980 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00242% 39/1,612,546 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,995
South Asian	0.00549%	18,206
Remaining individualsnot grpmax-eligible	0.0032%	31,236
European (non-Finnish)	0.00237%	42,136

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.Cys103=
Coding: c.309C>T
MANE Select: NM_000152
dbSNP: rs373307393
Type: single nucleotide variant
Location: chr17:80104895 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.32 · 19 PDB
Residue 103: an α-helix; a disulfide bond; a UniProt-annotated variant site (in iopd and lopd; loss of activity; shows enzyme localization primarily in the er-golgi compartment suggesting that mutation could affect the normal processing and stability of the enzyme); a UniProt-annotated variant site (in iopd); the p-type domain

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.Cys103Arg Likely pathogenic ★★ same residue
GAA p.Cys103Ter Pathogenic ★★ same residue
GAA p.Cys103Trp Pathogenic/Likely pathogenic ★★ same residue
GAA p.Cys103Tyr Likely pathogenic ★ 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

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-cys103 (accessed [today's date]).

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