Is PGAM2 p.Leu6Val (c.16C>G) pathogenic?

PGAM2 p.Leu6Val (c.16C>G) is classified Uncertain significance in PGAM2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-21). AlphaMissense: likely benign (0.1314); Rare (popmax 0.164%, mid); Associated with Inborn genetic diseases.

What condition is associated with PGAM2 p.Leu6Val (c.16C>G)?

PGAM2 p.Leu6Val (c.16C>G) is associated with Inborn genetic diseases, glycogen storage disease due to phosphoglycerate mutase deficiency (ClinVar).

How common is PGAM2 p.Leu6Val (c.16C>G) in the general population?

PGAM2 p.Leu6Val (c.16C>G) is rare (popmax 0.164%, mid) (gnomAD).

What do computational predictors say about PGAM2 p.Leu6Val (c.16C>G)?

AlphaMissense predicts likely benign (score 0.1314) — an in-silico prediction, not a clinical call.

PGAM2 p.Leu6Val

c.16C>G · rs750344114 · VCV1392561

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1314 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.164%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1314	likely benign
REVEL	0.374	indeterminate
SaProt	LLR -8.52	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 -2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,762 bp · p 0.7 · regional, not allelic
Overall
CADD	18.21	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 0.164% Middle Eastern · 10/6,084 alleles

Filtering AF 0.0891% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0678%

Overall 0.00713% 115/1,613,890 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.164%	608
South Asian	0.0856%	1,168
Remaining individualsnot grpmax-eligible	0.016%	6,249
Admixed American	0.00167%	60,000
European (non-Finnish)	0.00136%	73,753

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.Leu6Val
Coding: c.16C>G
MANE Select: NM_001014436 · reported on NM_000290
dbSNP: rs750344114
Type: single nucleotide variant
Location: chr7:44065514 (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-leu6val (accessed [today's date]).

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