Is PYGL p.Arg70Ser (c.208C>A) pathogenic?

PYGL p.Arg70Ser (c.208C>A) is classified Uncertain significance in PYGL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-22). AlphaMissense: likely pathogenic (0.834); Absent from gnomAD v4.1; Associated with glycogen storage disease VI.

What condition is associated with PYGL p.Arg70Ser (c.208C>A)?

PYGL p.Arg70Ser (c.208C>A) is associated with glycogen storage disease VI (ClinVar).

How common is PYGL p.Arg70Ser (c.208C>A) in the general population?

PYGL p.Arg70Ser (c.208C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PYGL p.Arg70Ser (c.208C>A)?

AlphaMissense predicts likely pathogenic (score 0.834) — an in-silico prediction, not a clinical call.

PYGL p.Arg70Ser

Q: How is Glycogen storage disease due to liver glycogen phosphorylase deficiency inherited?

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

c.208C>A · rs1555328661 · VCV946196

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.834 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glycogen storage disease VI

Computational evidence

Protein change
AlphaMissense	0.834	likely pathogenic
REVEL	0.777	moderately pathogenic-leaning
SaProt	LLR -10.99	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.83, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 39 kb · p 0.2 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PYGL
Protein: p.Arg70Ser
Coding: c.208C>A
MANE Select: NM_002863
dbSNP: rs1555328661
Type: single nucleotide variant
Location: chr14:50944196 (GRCh38)
Gene constraint: LOEUF 1.048 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.87 · 19 PDB
Residue 70: an α-helix

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

Disease context

glycogen storage disease VI — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycogen storage disease due to liver glycogen phosphorylase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

PYGL c.1404-1G>A Pathogenic/Likely pathogenic ★★ same condition
PYGL c.1620+1G>A Pathogenic/Likely pathogenic ★★ same condition
PYGL c.1620+1G>C Pathogenic ★★ same condition
PYGL c.1768+1G>A Pathogenic ★★ same condition
PYGL c.772+1G>A Pathogenic/Likely pathogenic ★★ same condition
PYGL p.Arg576Ter Pathogenic ★★ same condition
PYGL p.Arg94Ter Pathogenic ★★ same condition
PYGL p.Gln577Ter 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/pygl-p-arg70ser (accessed [today's date]).

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