Is PGAM2 p.Thr84Ser (c.251C>G) pathogenic?

PGAM2 p.Thr84Ser (c.251C>G) is classified Uncertain significance in PGAM2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-08-22). AlphaMissense: likely benign (0.1182); Very rare (popmax 0.0028%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PGAM2 p.Thr84Ser (c.251C>G)?

PGAM2 p.Thr84Ser (c.251C>G) is associated with Inborn genetic diseases, glycogen storage disease due to phosphoglycerate mutase deficiency (ClinVar).

How common is PGAM2 p.Thr84Ser (c.251C>G) in the general population?

PGAM2 p.Thr84Ser (c.251C>G) is very rare (popmax 0.0028%, nfe) (gnomAD).

What do computational predictors say about PGAM2 p.Thr84Ser (c.251C>G)?

AlphaMissense predicts likely benign (score 0.1182) — an in-silico prediction, not a clinical call.

PGAM2 p.Thr84Ser

c.251C>G · rs1279915046 · VCV2160937

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1182 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0028%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1182	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -4.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.6	GERP 0.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,762 bp · p 0.7 · regional, not allelic
Overall
CADD	19.15	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 0.0028% European (non-Finnish) · 33/1,180,052 alleles

Filtering AF 0.00199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00175%

Overall 0.00205% 33/1,613,584 alleles · very rare

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.Thr84Ser
Coding: c.251C>G
MANE Select: NM_001014436 · reported on NM_000290
dbSNP: rs1279915046
Type: single nucleotide variant
Location: chr7:44065279 (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-thr84ser (accessed [today's date]).

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