Is GAA p.Ala644= (c.1932C>T) pathogenic?

GAA p.Ala644= (c.1932C>T) is classified Likely benign in GAA (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-21). Very rare (popmax 0.00838%, amr); Associated with Cardiovascular phenotype.

What condition is associated with GAA p.Ala644= (c.1932C>T)?

GAA p.Ala644= (c.1932C>T) is associated with Cardiovascular phenotype, glycogen storage disease II (ClinVar).

How common is GAA p.Ala644= (c.1932C>T) in the general population?

GAA p.Ala644= (c.1932C>T) is very rare (popmax 0.00838%, amr) (gnomAD).

GAA p.Ala644=

c.1932C>T · rs746194098 · VCV387757

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00838%, amr)

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 -20	GERP -3.9
Overall
CADD	0.594	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00838% Admixed American · 5/59,700 alleles

Filtering AF 0.00325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00208%

Overall 0.00304% 49/1,610,446 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00838%	11,940
Remaining individualsnot grpmax-eligible	0.00481%	20,781
European (non-Finnish)	0.00314%	31,861
East Asian	0.00223%	44,838
South Asian	0.00221%	45,175
African / African-American	0.00133%	74,908

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.Ala644=
Coding: c.1932C>T
MANE Select: NM_000152
dbSNP: rs746194098
Type: single nucleotide variant
Location: chr17:80112919 (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.Ala644Pro Uncertain significance ★★ ⚠ same residue
GAA p.Ala644Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
GAA p.Ala644Val Uncertain significance ★ ⚠ same residue
GAA p.Ala644fs Likely pathogenic ★ same residue
GAA p.Ala644Asp 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

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-ala644 (accessed [today's date]).

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