Is GAA p.Asp616= (c.1848C>T) pathogenic?

GAA p.Asp616= (c.1848C>T) is classified Conflicting classifications of pathogenicity in GAA (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-02-01). Rare (popmax 0.165%, eas); Associated with Cardiovascular phenotype.

What condition is associated with GAA p.Asp616= (c.1848C>T)?

GAA p.Asp616= (c.1848C>T) is associated with Cardiovascular phenotype, glycogen storage disease II (ClinVar).

How common is GAA p.Asp616= (c.1848C>T) in the general population?

GAA p.Asp616= (c.1848C>T) is rare (popmax 0.165%, eas) (gnomAD).

GAA p.Asp616=

c.1848C>T · rs377175810 · VCV284449

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.165%, 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 -5.4	GERP -3.4
Overall
CADD	6.878	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.165% East Asian · 74/44,840 alleles

Filtering AF 0.135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.124%

Overall 0.00713% 115/1,611,940 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.165%	606
African / African-American	0.0333%	3,002
Admixed American	0.00835%	11,974
Remaining individualsnot grpmax-eligible	0.0032%	31,219
South Asian	0.0011%	90,810
European (non-Finnish)	0.000678%	147,449

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.Asp616=
Coding: c.1848C>T
MANE Select: NM_000152
dbSNP: rs377175810
Type: single nucleotide variant
Location: chr17:80112671 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.32 · 19 PDB
Residue 616: a binding site

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.Asp616Tyr Likely pathogenic ★★ same residue
GAA p.Asp616His Likely pathogenic ★ same residue
GAA p.Asp616Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
GAA p.Asp616Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
GAA p.Asp616fs Pathogenic ★★ same residue
GAA p.Asp616Gly Uncertain significance ★ ⚠ same residue
GAA c.1076-1G>C Pathogenic ★★★ same condition
GAA c.1076-22T>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-asp616 (accessed [today's date]).

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