Is PGAM2 p.Ile171Val (c.511A>G) pathogenic?

PGAM2 p.Ile171Val (c.511A>G) is classified Conflicting classifications of pathogenicity in PGAM2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-28). AlphaMissense: likely benign (0.2037); Rare (popmax 0.221%, amr); Associated with glycogen storage disease due to phosphoglycerate mutase deficiency.

What condition is associated with PGAM2 p.Ile171Val (c.511A>G)?

PGAM2 p.Ile171Val (c.511A>G) is associated with glycogen storage disease due to phosphoglycerate mutase deficiency (ClinVar).

How common is PGAM2 p.Ile171Val (c.511A>G) in the general population?

PGAM2 p.Ile171Val (c.511A>G) is rare (popmax 0.221%, amr) (gnomAD).

What do computational predictors say about PGAM2 p.Ile171Val (c.511A>G)?

AlphaMissense predicts likely benign (score 0.2037) — an in-silico prediction, not a clinical call.

PGAM2 p.Ile171Val

Q: How is Glycogen storage disease due to phosphoglycerate mutase deficiency inherited?

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

c.511A>G · rs372452057 · VCV432232

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2037 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.221%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

glycogen storage disease due to phosphoglycerate mutase deficiency

Computational evidence

Protein change
AlphaMissense	0.2037	likely benign
REVEL	0.41	indeterminate
SaProt	LLR -9.34	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,762 bp · p 0.7 · regional, not allelic
Overall
CADD	23.6	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

Grpmax group 0.221% Admixed American · 132/59,758 alleles

Filtering AF 0.19% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.179%

Overall 0.00833% 134/1,609,044 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.221%	453
Remaining individualsnot grpmax-eligible	0.0016%	62,324
European (non-Finnish)	8.48e-05%	1,178,692

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: PGAM2
Protein: p.Ile171Val
Coding: c.511A>G
MANE Select: NM_001014436 · reported on NM_000290
dbSNP: rs372452057
Type: single nucleotide variant
Location: chr7:44064916 (GRCh38)

Full PGAM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

glycogen storage disease due to phosphoglycerate mutase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycogen storage disease due to phosphoglycerate mutase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood

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/pgam2-p-ile171val (accessed [today's date]).

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