Is PGM2 p.Arg48Gln (c.143G>A) pathogenic?

PGM2 p.Arg48Gln (c.143G>A) is classified Likely benign in PGM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-26). AlphaMissense: likely benign (0.0767); Very rare (popmax 0.00267%, afr).

How common is PGM2 p.Arg48Gln (c.143G>A) in the general population?

PGM2 p.Arg48Gln (c.143G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about PGM2 p.Arg48Gln (c.143G>A)?

AlphaMissense predicts likely benign (score 0.0767) — an in-silico prediction, not a clinical call.

PGM2 p.Arg48Gln

c.143G>A · rs201598002 · VCV2469023

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0767 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0767	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -8.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -3.1, phastCons 0.036
Regional constraint	o/e 0.99	unconstrained · MANE · 18 kb · p 0.87 · regional, not allelic
Overall
CADD	14.87	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 0.00267% African / African-American · 2/74,860 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000809% 13/1,607,900 alleles · very rare exomes 11/1,455,740 · genomes 2/152,160 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00322%	31,058
African / African-Americangrpmax	0.00267%	37,430
South Asian	0.00222%	45,102
Admixed American	0.0017%	58,674
European (non-Finnish)	0.00051%	196,202

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg48Gln
Coding: c.143G>A
MANE Select: NM_018290
dbSNP: rs201598002
Type: single nucleotide variant
Location: chr4:37830025 (GRCh38)
Gene constraint: LOEUF 1.172 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.60

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-arg48gln (accessed [today's date]).

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