Is PGAM2 p.Arg240Trp (c.718C>T) pathogenic?

PGAM2 p.Arg240Trp (c.718C>T) is classified Uncertain significance in PGAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-24). AlphaMissense: ambiguous (0.4844); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with PGAM2 p.Arg240Trp (c.718C>T)?

PGAM2 p.Arg240Trp (c.718C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PGAM2 p.Arg240Trp (c.718C>T) in the general population?

PGAM2 p.Arg240Trp (c.718C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about PGAM2 p.Arg240Trp (c.718C>T)?

AlphaMissense predicts ambiguous (score 0.4844) — an in-silico prediction, not a clinical call.

PGAM2 p.Arg240Trp

c.718C>T · VCV3931104

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4844 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4844	ambiguous
REVEL	0.605	indeterminate
SaProt	LLR -15.04	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	26.7	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 0.00167% Admixed American · 1/60,002 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00062% 10/1,614,016 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,002
African / African-American	0.00134%	74,904
European (non-Finnish)	0.000678%	147,504

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.Arg240Trp
Coding: c.718C>T
MANE Select: NM_001014436 · reported on NM_000290
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-arg240trp (accessed [today's date]).

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