Is PGAM2 p.Val82Leu (c.244G>T) pathogenic?

PGAM2 p.Val82Leu (c.244G>T) is classified Uncertain significance in PGAM2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-30). AlphaMissense: likely benign (0.2593); Ultra-rare (popmax 0.0136%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PGAM2 p.Val82Leu (c.244G>T)?

PGAM2 p.Val82Leu (c.244G>T) is associated with Inborn genetic diseases, glycogen storage disease due to phosphoglycerate mutase deficiency (ClinVar).

How common is PGAM2 p.Val82Leu (c.244G>T) in the general population?

PGAM2 p.Val82Leu (c.244G>T) is ultra-rare (popmax 0.0136%, nfe) (gnomAD).

What do computational predictors say about PGAM2 p.Val82Leu (c.244G>T)?

AlphaMissense predicts likely benign (score 0.2593) — an in-silico prediction, not a clinical call.

PGAM2 p.Val82Leu

c.244G>T · rs528467394 · VCV360278

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2593 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0136%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2593	likely benign
REVEL	0.304	indeterminate
SaProt	LLR -8.51	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 3.7	GERP 0.72, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,762 bp · p 0.7 · regional, not allelic
Overall
CADD	18.42	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0136% European (non-Finnish) · 160/1,180,062 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.01% 162/1,613,560 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0136%	7,375
Remaining individualsnot grpmax-eligible	0.0016%	62,478
African / African-American	0.00133%	74,936

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.Val82Leu
Coding: c.244G>T
MANE Select: NM_001014436 · reported on NM_000290
dbSNP: rs528467394
Type: single nucleotide variant
Location: chr7:44065286 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: glycogen storage disease due to phosphoglycerate mutase deficiency

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-val82leu (accessed [today's date]).

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