Is GAA p.Arg168= (c.502C>A) pathogenic?

GAA p.Arg168= (c.502C>A) is classified Likely benign in GAA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-04-03). Very rare (popmax 0.00439%, sas); Associated with Cardiovascular phenotype.

What condition is associated with GAA p.Arg168= (c.502C>A)?

GAA p.Arg168= (c.502C>A) is associated with Cardiovascular phenotype, glycogen storage disease II (ClinVar).

How common is GAA p.Arg168= (c.502C>A) in the general population?

GAA p.Arg168= (c.502C>A) is very rare (popmax 0.00439%, sas) (gnomAD).

GAA p.Arg168=

c.502C>A · rs777473001 · VCV1744882

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

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 4	GERP 0.14, phastCons 0.57
Overall
CADD	8.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,086 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000343% 5/1,459,752 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,772
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Arg168=
Coding: c.502C>A
MANE Select: NM_000152
dbSNP: rs777473001
Type: single nucleotide variant
Location: chr17:80105088 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.32 · 19 PDB
Residue 168: a β-strand

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.Arg168Leu Uncertain significance ★★ ⚠ same residue
GAA p.Arg168Trp Uncertain significance ★★ ⚠ same residue
GAA p.Arg168Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
GAA p.Arg168Pro Conflicting classifications of pathogenicity ★ ⚠ 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

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-arg168 (accessed [today's date]).

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