Is GAA p.Pro361= (c.1083G>A) pathogenic?

GAA p.Pro361= (c.1083G>A) is classified Likely benign in GAA (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-11). Ultra-rare (popmax 0.0164%, mid); Associated with Cardiovascular phenotype.

What condition is associated with GAA p.Pro361= (c.1083G>A)?

GAA p.Pro361= (c.1083G>A) is associated with Cardiovascular phenotype, glycogen storage disease II (ClinVar).

How common is GAA p.Pro361= (c.1083G>A) in the general population?

GAA p.Pro361= (c.1083G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

GAA p.Pro361=

c.1083G>A · rs781379047 · VCV501028

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Cardiovascular phenotype

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 -8.2	GERP -3.5
Overall
CADD	4.198	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 0.00546% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00506%

Overall 0.00558% 90/1,612,952 alleles · ultra-rare exomes 87/1,460,762 · genomes 3/152,190 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Admixed American	0.01%	9,998
European (non-Finnish)	0.0067%	14,936
East Asian	0.00446%	22,445
Remaining individualsnot grpmax-eligible	0.0016%	62,454
South Asian	0.0011%	91,094

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.Pro361=
Coding: c.1083G>A
MANE Select: NM_000152
dbSNP: rs781379047
Type: single nucleotide variant
Location: chr17:80108496 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.32 · 19 PDB
Residue 361: an α-helix; a UniProt-annotated variant site (in lopd)

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: glycogen storage disease II

Similar variants

GAA p.Pro361Arg Likely pathogenic ★★★ same residue
GAA p.Pro361Leu Pathogenic ★★★ same residue
GAA p.Pro361Gln 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-pro361 (accessed [today's date]).

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