Is PGAM2 p.Thr15= (c.45A>T) pathogenic?

PGAM2 p.Thr15= (c.45A>T) is classified Likely benign in PGAM2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-09-28). Ultra-rare (popmax 0.0253%, afr); Associated with PGAM2-related disorder.

What condition is associated with PGAM2 p.Thr15= (c.45A>T)?

PGAM2 p.Thr15= (c.45A>T) is associated with PGAM2-related disorder (ClinVar).

How common is PGAM2 p.Thr15= (c.45A>T) in the general population?

PGAM2 p.Thr15= (c.45A>T) is ultra-rare (popmax 0.0253%, afr) (gnomAD).

PGAM2 p.Thr15=

c.45A>T · rs142350623 · VCV3053583

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, afr)

Conditions

PGAM2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -3.3	GERP -3.7
Overall
CADD	12.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0253% African / African-American · 19/75,062 alleles

Filtering AF 0.0165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00142% 23/1,614,134 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0253%	3,951
Remaining individualsnot grpmax-eligible	0.0064%	15,627

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.Thr15=
Coding: c.45A>T
MANE Select: NM_001014436 · reported on NM_000290
dbSNP: rs142350623
Type: single nucleotide variant
Location: chr7:44065485 (GRCh38)

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

Disease context

PGAM2-related disorder

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-thr15 (accessed [today's date]).

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