Is PYGM p.Pro382Ala (c.1144C>G) pathogenic?

PYGM p.Pro382Ala (c.1144C>G) is classified Uncertain significance in PYGM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-02). AlphaMissense: likely pathogenic (0.5909); Very rare (popmax 0.00509%, amr); Associated with glycogen storage disease V.

What condition is associated with PYGM p.Pro382Ala (c.1144C>G)?

PYGM p.Pro382Ala (c.1144C>G) is associated with glycogen storage disease V (ClinVar).

How common is PYGM p.Pro382Ala (c.1144C>G) in the general population?

PYGM p.Pro382Ala (c.1144C>G) is very rare (popmax 0.00509%, amr) (gnomAD).

What do computational predictors say about PYGM p.Pro382Ala (c.1144C>G)?

AlphaMissense predicts likely pathogenic (score 0.5909) — an in-silico prediction, not a clinical call.

PYGM p.Pro382Ala

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.1144C>G · rs1371878710 · VCV2671931

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5909 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00509%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glycogen storage disease V

Computational evidence

Protein change
AlphaMissense	0.5909	likely pathogenic
REVEL	0.806	moderately pathogenic-leaning
SaProt	LLR -11.01	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 2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 13 kb · p 0.00017 · regional, not allelic
Overall
CADD	26.0	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

Grpmax group 0.00509% Admixed American · 3/58,954 alleles

Filtering AF 0.00135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000674%

Overall 0.00081% 13/1,605,502 alleles · very rare exomes 1/1,453,706 · genomes 12/151,796 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00509%	19,651
Finnishnot grpmax-eligible	0.00159%	62,964
African / African-American	0.00134%	74,754
South Asian	0.00112%	89,606
European (non-Finnish)	0.000595%	168,000

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: PYGM
Protein: p.Pro382Ala
Coding: c.1144C>G
MANE Select: NM_005609
dbSNP: rs1371878710
Type: single nucleotide variant
Location: chr11:64753974 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.41 · 1 PDB
Residue 382: a UniProt-annotated variant site (in gsd5); an α-helix

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 p.Pro382Leu Uncertain significance ★ ⚠ same residue
PYGM p.Pro382= Likely benign ★ same residue
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

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-pro382ala (accessed [today's date]).

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