Is GAA p.Asp356= (c.1068C>T) pathogenic?

GAA p.Asp356= (c.1068C>T) is classified Likely benign in GAA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-23). Ultra-rare (popmax 0.0231%, sas); Associated with Cardiovascular phenotype.

What condition is associated with GAA p.Asp356= (c.1068C>T)?

GAA p.Asp356= (c.1068C>T) is associated with Cardiovascular phenotype, glycogen storage disease II (ClinVar).

How common is GAA p.Asp356= (c.1068C>T) in the general population?

GAA p.Asp356= (c.1068C>T) is ultra-rare (popmax 0.0231%, sas) (gnomAD).

GAA p.Asp356=

c.1068C>T · rs751215137 · VCV783175

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP -8.9	GERP -3.8
Overall
CADD	0.956	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0231% South Asian · 21/91,096 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.00285% 46/1,613,278 alleles · ultra-rare exomes 43/1,461,060 · genomes 3/152,218 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0231%	4,338
Admixed American	0.005%	20,001
Remaining individualsnot grpmax-eligible	0.0032%	31,239
European (non-Finnish)	0.00169%	59,002

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.Asp356=
Coding: c.1068C>T
MANE Select: NM_000152
dbSNP: rs751215137
Type: single nucleotide variant
Location: chr17:80108402 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.32 · 19 PDB
Residue 356: an α-helix

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 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
GAA c.1438-1G>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-asp356 (accessed [today's date]).

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