# NM_000290.4(PGAM2):c.441C>T (p.Pro147=)

https://sugi.bio/variant/pgam2-p-pro147

## Summary

**PGAM2 p.Pro147= (c.441C>T)** is classified **Likely benign** in PGAM2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-26). Ultra-rare (popmax 0.0117%, amr); Associated with glycogen storage disease due to phosphoglycerate mutase deficiency.

**At a glance:** Likely benign · review: Multiple submitters · rsID rs373213851 · 3 submitters · 1 linked condition · ultra-rare (popmax 0.0117%, amr)

## For patients & families {#patients}

This is a change in the PGAM2 gene that is classified as likely benign — not considered disease-causing, submitted by 3 submitters, and is linked to glycogen storage disease due to phosphoglycerate mutase deficiency.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

|  |  |
| --- | --- |
| Typical inheritance (of this condition) | Autosomal recessive |
| Age of onset (of this condition) | Adolescent, Childhood |
| Clinical trials | 1 registered for this condition — see ClinicalTrials.gov |

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0009964/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [PGAM2](https://sugi.bio/atlas/gene/PGAM2/) |
| Protein change (HGVS p.) | p.Pro147= |
| Coding change (HGVS c.) | c.441C>T |
| MANE Select transcript | [NM_001014436](https://www.ncbi.nlm.nih.gov/nuccore/NM_001014436) (variant reported on NM_000290) |
| dbSNP | [rs373213851](https://www.ncbi.nlm.nih.gov/snp/rs373213851/) |
| Variant type | single nucleotide variant |
| Location | chr7:44064986-44064986 (GRCh38) |
| ClinVar | [VCV2182447](https://www.ncbi.nlm.nih.gov/clinvar/variation/2182447/) |

**All HGVS expressions:** `NC_000007.13:g.44104585G>A`, `NC_000007.14:g.44064986G>A`, `NG_013016.1:g.5602C>T`, `NG_177787.1:g.183G>A`, `NM_000290.4:c.441C>T`, `NM_001014436.3:c.*4070G>A`, `NM_001122956.2:c.*4070G>A`, `NM_001284313.2:c.*4070G>A`, `NM_001284315.2:c.*4070G>A`, `NM_001362723.2:c.*4070G>A`, `NM_014063.7:c.*4070G>A`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP -14.036, GERP -3.69 — fast-evolving / accelerated position
- CADD: **PHRED 0.073**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI: **not looked up on this page** — it was served without the gene's SpliceAI index, so no lookup was made. This is a gap in this page, not in the data, and says nothing about whether a splicing effect is predicted.
- Population frequency (gnomAD v4.1): grpmax **0.0117%** (amr) · FAF95 0.00673% · FAF99 0.00625% · 7/59,858 in the highest group · 188/1,606,572 alleles overall — ultra-rare (popmax 0.0117%, amr).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Finnish (not grpmax-eligible) | 0.118% | 847 |
| Remaining individuals (not grpmax-eligible) | 0.0144% | 6,934 |
| Admixed American (grpmax) | 0.0117% | 8,551 |
| European (non-Finnish) | 0.00805% | 12,416 |
| East Asian | 0.00669% | 14,954 |
| Ashkenazi Jewish (not grpmax-eligible) | 0.00339% | 29,534 |
| South Asian | 0.0033% | 30,289 |
| African / African-American | 0.00267% | 37,450 |

Finnish shows a higher raw frequency than the grpmax group. 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.

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Clinical significance {#significance}

**Likely benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2025-12-26.

**Submitter consensus:** unanimous (3/3 Likely benign).

**Submission history:** 3 submissions (2024–2025); classifications have been stable.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2025-12-26 |
| CeGaT Center for Human Genetics Tuebingen | Likely benign | criteria provided, single submitter | clinical testing | 2024-10-01 |
| Blueprint Genetics | Likely benign | criteria provided, single submitter | clinical testing | 2024-03-18 |

## Associated conditions {#conditions}

[glycogen storage disease due to phosphoglycerate mutase deficiency](https://sugi.bio/atlas/disease/glycogen-storage-disease-due-to-phosphoglycerate-mutase-deficiency/).

**Reported phenotype names (ClinVar):** Glycogen storage disease type X, not provided, not specified, none provided, AllHighlyPenetrant, Dimauro disease, PGAMM DEFICIENCY, PHOSPHOGLYCERATE MUTASE, MUSCLE, DEFICIENCY OF, GSD X, MYOPATHY DUE TO PHOSPHOGLYCERATE MUTASE DEFICIENCY.

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-07-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 2182447). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*