Is GAA p.Pro347Ser (c.1039C>T) pathogenic?

GAA p.Pro347Ser (c.1039C>T) is classified Uncertain significance in GAA (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-11). AlphaMissense: ambiguous (0.5589); Absent from gnomAD v4.1; Associated with glycogen storage disease II.

What condition is associated with GAA p.Pro347Ser (c.1039C>T)?

GAA p.Pro347Ser (c.1039C>T) is associated with glycogen storage disease II (ClinVar).

How common is GAA p.Pro347Ser (c.1039C>T) in the general population?

GAA p.Pro347Ser (c.1039C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GAA p.Pro347Ser (c.1039C>T)?

AlphaMissense predicts ambiguous (score 0.5589) — an in-silico prediction, not a clinical call.

GAA p.Pro347Ser

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.1039C>T · rs2039144354 · VCV1002609

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5589 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

glycogen storage disease II

Computational evidence

Protein change
AlphaMissense	0.5589	ambiguous
REVEL	0.882	moderately pathogenic-leaning
SaProt	LLR -12.82	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 15 kb · p 0.22 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GAA
Protein: p.Pro347Ser
Coding: c.1039C>T
MANE Select: NM_000152
dbSNP: rs2039144354
Type: single nucleotide variant
Location: chr17:80108373 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.32 · 19 PDB
Residue 347: an α-helix; a UniProt-annotated variant site (in iopd)

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.Pro347Arg Likely pathogenic ★ same residue
GAA p.Pro347= Likely benign ★ 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
GAA c.1437+1G>A Likely 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-pro347ser (accessed [today's date]).

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