Is G6PC1 p.Pro84= (c.252A>G) pathogenic?

G6PC1 p.Pro84= (c.252A>G) is classified Likely benign in G6PC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-07). Very rare (popmax 8.48e-05%, nfe); Associated with glycogen storage disease due to glucose-6-phosphatase deficiency type IA.

What condition is associated with G6PC1 p.Pro84= (c.252A>G)?

G6PC1 p.Pro84= (c.252A>G) is associated with glycogen storage disease due to glucose-6-phosphatase deficiency type IA (ClinVar).

How common is G6PC1 p.Pro84= (c.252A>G) in the general population?

G6PC1 p.Pro84= (c.252A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

G6PC1 p.Pro84=

Q: How is Glycogen storage disease due to glucose-6-phosphatase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.252A>G · rs148967047 · VCV1095550

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

glycogen storage disease due to glucose-6-phosphatase deficiency type IA

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 -9.9	GERP -3.9
Overall
CADD	0.211	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,368 alleles

Overall 6.2e-05% 1/1,613,450 alleles · very rare exomes 1/1,461,152 · genomes 0/152,298 · joint denominator

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: G6PC1
Protein: p.Pro84=
Coding: c.252A>G
MANE Select: NM_000151
dbSNP: rs148967047
Type: single nucleotide variant
Location: chr17:42903952 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.21 · 6 PDB
Residue 84: a turn

Full G6PC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

glycogen storage disease due to glucose-6-phosphatase deficiency type IA — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycogen storage disease due to glucose-6-phosphatase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

G6PC1 p.Pro84Ser Uncertain significance ★ ⚠ same residue
G6PC1 p.Pro84fs Likely pathogenic ★ same residue
G6PC1 c.230+1G>C Pathogenic/Likely pathogenic ★★ same condition
G6PC1 c.231-1G>A Pathogenic ★★ same condition
G6PC1 c.447-1G>C Likely pathogenic ★★ same condition
G6PC1 c.563-3C>G Pathogenic/Likely pathogenic ★★ same condition
G6PC1 p.Ala124Thr Pathogenic/Likely pathogenic ★★ same condition
G6PC1 p.Ala274Thr 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/g6pc1-p-pro84 (accessed [today's date]).

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