Is PYGM p.Pro232Ala (c.694C>G) pathogenic?

PYGM p.Pro232Ala (c.694C>G) is classified Uncertain significance in PYGM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-04). AlphaMissense: ambiguous (0.473); Absent from gnomAD v4.1; Associated with glycogen storage disease V.

What condition is associated with PYGM p.Pro232Ala (c.694C>G)?

PYGM p.Pro232Ala (c.694C>G) is associated with glycogen storage disease V (ClinVar).

How common is PYGM p.Pro232Ala (c.694C>G) in the general population?

PYGM p.Pro232Ala (c.694C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PYGM p.Pro232Ala (c.694C>G)?

AlphaMissense predicts ambiguous (score 0.473) — an in-silico prediction, not a clinical call.

PYGM p.Pro232Ala

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

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

c.694C>G · rs2496664048 · VCV2173311

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.473 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

glycogen storage disease V

Computational evidence

Protein change
AlphaMissense	0.473	ambiguous
REVEL	0.786	moderately pathogenic-leaning
SaProt	LLR -13.11	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 13 kb · p 0.00017 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

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: PYGM
Protein: p.Pro232Ala
Coding: c.694C>G
MANE Select: NM_005609
dbSNP: rs2496664048
Type: single nucleotide variant
Location: chr11:64755525 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.41 · 1 PDB
Residue 232: a UniProt-annotated variant site (in gsd5); a β-strand

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

Disease context

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

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

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

Similar variants

PYGM c.1092+1G>A Likely pathogenic ★★ same condition
PYGM c.1092+1G>C Likely pathogenic ★★ same condition
PYGM c.1239+1G>A Pathogenic/Likely pathogenic ★★ same condition
PYGM c.1240-2A>G Likely pathogenic ★★ same condition
PYGM c.1403+1G>A Pathogenic ★★ same condition
PYGM c.1768+1G>A Pathogenic/Likely pathogenic ★★ same condition
PYGM c.1768+2T>G Pathogenic/Likely pathogenic ★★ same condition
PYGM c.1827+1G>C 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/pygm-p-pro232ala (accessed [today's date]).

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