Is PGAM2 p.Arg240Gly (c.718C>G) pathogenic?

PGAM2 p.Arg240Gly (c.718C>G) is classified Uncertain significance in PGAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-04). AlphaMissense: ambiguous (0.4278); Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with PGAM2 p.Arg240Gly (c.718C>G)?

PGAM2 p.Arg240Gly (c.718C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PGAM2 p.Arg240Gly (c.718C>G) in the general population?

PGAM2 p.Arg240Gly (c.718C>G) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about PGAM2 p.Arg240Gly (c.718C>G)?

AlphaMissense predicts ambiguous (score 0.4278) — an in-silico prediction, not a clinical call.

PGAM2 p.Arg240Gly

c.718C>G · rs375024229 · VCV2321702

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4278 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4278	ambiguous
REVEL	0.487	indeterminate
SaProt	LLR -12.61	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.4	GERP 0.66, phastCons 0.98
Regional constraint	o/e 0.98	unconstrained · MANE · 2,762 bp · p 0.7 · regional, not allelic
Overall
CADD	23.3	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 0.005% Admixed American · 3/60,022 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000342% 5/1,461,886 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,007
European (non-Finnish)	0.000169%	590,009

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.Arg240Gly
Coding: c.718C>G
MANE Select: NM_001014436 · reported on NM_000290
dbSNP: rs375024229
Type: single nucleotide variant
Location: chr7:44062808 (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

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-arg240gly (accessed [today's date]).

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