Is GAA p.Ser688= (c.2064C>T) pathogenic?

GAA p.Ser688= (c.2064C>T) is classified Conflicting classifications of pathogenicity in GAA (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-03-31). Very rare (popmax 0.00226%, eas); Associated with Cardiovascular phenotype.

What condition is associated with GAA p.Ser688= (c.2064C>T)?

GAA p.Ser688= (c.2064C>T) is associated with Cardiovascular phenotype, glycogen storage disease II (ClinVar).

How common is GAA p.Ser688= (c.2064C>T) in the general population?

GAA p.Ser688= (c.2064C>T) is very rare (popmax 0.00226%, eas) (gnomAD).

GAA p.Ser688=

c.2064C>T · rs140996643 · VCV287992

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00226%, eas)

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 -2.1	GERP 1.3
Overall
CADD	7.355	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00226% East Asian · 1/44,288 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000833%

Overall 0.0015% 24/1,600,990 alleles · very rare exomes 23/1,448,740 · genomes 1/152,250 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00226%	44,288
South Asian	0.00225%	44,377
Admixed American	0.00171%	58,430
European (non-Finnish)	0.00162%	61,839
African / African-American	0.00134%	74,776

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.Ser688=
Coding: c.2064C>T
MANE Select: NM_000152
dbSNP: rs140996643
Type: single nucleotide variant
Location: chr17:80113241 (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

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

Also linked: glycogen storage disease II

Similar variants

GAA p.Ser688Arg 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
GAA c.1437+1G>A Likely pathogenic ★★★ same condition
GAA c.1437+2T>C 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-ser688 (accessed [today's date]).

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