Is PGM2 p.Pro148Ser (c.442C>T) pathogenic?

PGM2 p.Pro148Ser (c.442C>T) is classified Uncertain significance in PGM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). AlphaMissense: ambiguous (0.3719); Ultra-rare (popmax 0.0673%, eas).

How common is PGM2 p.Pro148Ser (c.442C>T) in the general population?

PGM2 p.Pro148Ser (c.442C>T) is ultra-rare (popmax 0.0673%, eas) (gnomAD).

What do computational predictors say about PGM2 p.Pro148Ser (c.442C>T)?

AlphaMissense predicts ambiguous (score 0.3719) — an in-silico prediction, not a clinical call.

PGM2 p.Pro148Ser

c.442C>T · VCV4135363

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3719 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0673%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3719	ambiguous
REVEL	0.283	benign-leaning
SaProt	LLR -6.67	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 18 kb · p 0.87 · regional, not allelic
Overall
CADD	23.4	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 0.0673% East Asian · 30/44,586 alleles

Filtering AF 0.0484% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.042%

Overall 0.00206% 32/1,549,668 alleles · ultra-rare exomes 31/1,397,530 · genomes 1/152,138 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0673%	1,486
Remaining individualsnot grpmax-eligible	0.00166%	60,410
European (non-Finnish)	8.92e-05%	1,121,650

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.Pro148Ser
Coding: c.442C>T
MANE Select: NM_018290
Type: single nucleotide variant
Location: chr4:37839848 (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-pro148ser (accessed [today's date]).

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