Is GAA p.Pro787fs (c.2360del) pathogenic?

GAA p.Pro787fs (c.2360del) is classified Likely pathogenic in GAA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-31). Very rare (popmax 6.2e-05%); Associated with GAA-related disorders.

What condition is associated with GAA p.Pro787fs (c.2360del)?

GAA p.Pro787fs (c.2360del) is associated with GAA-related disorders (ClinVar).

How common is GAA p.Pro787fs (c.2360del) in the general population?

GAA p.Pro787fs (c.2360del) is very rare (popmax 6.2e-05%) (gnomAD).

GAA p.Pro787fs

c.2360del · VCV4937373

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Conditions

GAA-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 17 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.03	GERP -0.77, phastCons 0.004
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,612,596 alleles · very rare exomes 0/1,460,554 · genomes 1/152,042 · joint denominator

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.Pro787fs
Coding: c.2360del
MANE Select: NM_000152
Type: Deletion
Location: chr17:80117626 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.32 · 19 PDB

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

Disease context

GAA-related disorders

Similar variants

GAA p.Ser349fs Pathogenic ★★ same condition
GAA p.Pro787Thr Uncertain significance ★ ⚠ same residue
GAA p.Pro787= Likely benign ★ same residue
GAA c.1438-1G>T Pathogenic/Likely pathogenic ★★ same condition
GAA p.Ala691fs Pathogenic ★★ same condition
GAA p.Leu574Pro Pathogenic/Likely pathogenic ★★ same condition
GAA p.Arg422Trp Uncertain significance ★★ ⚠ same condition
GAA c.955+2T>C 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-pro787fs (accessed [today's date]).

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