Is G6PC1 p.Pro334= (c.1002C>T) pathogenic?

G6PC1 p.Pro334= (c.1002C>T) is classified Benign/Likely benign in G6PC1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-20). Ultra-rare (popmax 0.044%, afr); Associated with glycogen storage disease due to glucose-6-phosphatase deficiency type IA.

What condition is associated with G6PC1 p.Pro334= (c.1002C>T)?

G6PC1 p.Pro334= (c.1002C>T) is associated with glycogen storage disease due to glucose-6-phosphatase deficiency type IA (ClinVar).

How common is G6PC1 p.Pro334= (c.1002C>T) in the general population?

G6PC1 p.Pro334= (c.1002C>T) is ultra-rare (popmax 0.044%, afr) (gnomAD).

G6PC1 p.Pro334=

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.1002C>T · rs143991162 · VCV377898

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.044%, afr)

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 0.015	GERP -3.7, phastCons 0.07
Overall
CADD	8.307	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.044% African / African-American · 33/75,044 alleles

Filtering AF 0.0321% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0281%

Overall 0.0039% 63/1,614,158 alleles · ultra-rare exomes 34/1,461,886 · genomes 29/152,272 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.044%	2,274
Admixed American	0.0383%	2,610
Remaining individualsnot grpmax-eligible	0.0096%	10,418
South Asian	0.0011%	91,066

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.Pro334=
Coding: c.1002C>T
MANE Select: NM_000151
dbSNP: rs143991162
Type: single nucleotide variant
Location: chr17:42911354 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.21 · 6 PDB
Residue 334: an α-helix

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 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
G6PC1 p.Ala274Val Pathogenic/Likely pathogenic ★★ same condition
G6PC1 p.Ala65Pro Pathogenic/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-pro334 (accessed [today's date]).

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