Is G6PC1 p.Ser136= (c.408C>T) pathogenic?

G6PC1 p.Ser136= (c.408C>T) is classified Uncertain significance in G6PC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-11). Ultra-rare (popmax 0.011%, sas); Associated with glycogen storage disease due to glucose-6-phosphatase deficiency type IA.

What condition is associated with G6PC1 p.Ser136= (c.408C>T)?

G6PC1 p.Ser136= (c.408C>T) is associated with glycogen storage disease due to glucose-6-phosphatase deficiency type IA (ClinVar).

How common is G6PC1 p.Ser136= (c.408C>T) in the general population?

G6PC1 p.Ser136= (c.408C>T) is ultra-rare (popmax 0.011%, sas) (gnomAD).

G6PC1 p.Ser136=

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.408C>T · rs1469161155 · VCV1923859

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

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/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Pangolin	Δ0.42	gain · loss 0.03 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.44	GERP -3.9, phastCons 0.087
Overall
CADD	3.503	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/91,042 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.000682% 11/1,613,812 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,104
Admixed American	0.00167%	59,994

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.Ser136=
Coding: c.408C>T
MANE Select: NM_000151
dbSNP: rs1469161155
Type: single nucleotide variant
Location: chr17:42907590 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.21 · 6 PDB
Residue 136: 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-ser136 (accessed [today's date]).

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