Is PGM2 p.Glu488Asp (c.1464A>C) pathogenic?

PGM2 p.Glu488Asp (c.1464A>C) is classified Benign in PGM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-07). AlphaMissense: likely benign (0.0769); Common (popmax 18.6%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about PGM2 p.Glu488Asp (c.1464A>C)?

AlphaMissense predicts likely benign (score 0.0769) — an in-silico prediction, not a clinical call.

PGM2 p.Glu488Asp

Q: How common is PGM2 p.Glu488Asp (c.1464A>C) in the general population?

PGM2 p.Glu488Asp (c.1464A>C) is common (popmax 18.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1464A>C · VCV4684784

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0769 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 18.6%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0769	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -6.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.12	GERP -4.1
Regional constraint	o/e 0.97	unconstrained · MANE · 17 kb · p 0.53 · regional, not allelic
Overall
CADD	8.828	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 18.6% African / African-American · 13,482/72,616 alleles

Filtering AF 18.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.2%

Overall 3.69% 58,332/1,581,802 alleles · common exomes 45,838/1,429,558 · genomes 12,494/152,244 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	18.6%	5
East Asian	15%	7
Admixed American	13.2%	8
Remaining individualsnot grpmax-eligible	4.88%	21
South Asian	3.23%	31
Middle Eastern	3.06%	33
Ashkenazi Jewishnot grpmax-eligible	2.96%	34
Finnishnot grpmax-eligible	2.51%	40
European (non-Finnish)	1.98%	51
Amishnot grpmax-eligible	0.219%	456

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: PGM2
Protein: p.Glu488Asp
Coding: c.1464A>C
MANE Select: NM_018290
Type: single nucleotide variant
Location: chr4:37850235 (GRCh38)
Gene constraint: LOEUF 1.172 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.60
Residue 488: a UniProt-annotated variant site (in)

Full PGM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PGM2 p.Asp322= Benign ★★ same type
PGM2 p.Ala107Thr Uncertain significance ★ ⚠ same type
PGM2 p.Ala121Val Uncertain significance ★ ⚠ same type
PGM2 p.Ala124Thr Uncertain significance ★ ⚠ same type
PGM2 p.Ala277Val Uncertain significance ★ ⚠ same type
PGM2 p.Ala2Gly Uncertain significance ★ ⚠ same type
PGM2 p.Ala310Asp Uncertain significance ★ ⚠ same type
PGM2 p.Ala315Asp Uncertain significance ★ ⚠ same type

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/pgm2-p-glu488asp (accessed [today's date]).

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