Is PMM2 p.Pro20= (c.60G>A) pathogenic?

PMM2 p.Pro20= (c.60G>A) is classified Likely benign in PMM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-30). No allele count reported in gnomAD v4.1 (AN 1,605,720); Associated with PMM2-congenital disorder of glycosylation.

What condition is associated with PMM2 p.Pro20= (c.60G>A)?

PMM2 p.Pro20= (c.60G>A) is associated with PMM2-congenital disorder of glycosylation (ClinVar).

How common is PMM2 p.Pro20= (c.60G>A) in the general population?

PMM2 p.Pro20= (c.60G>A) is no allele count reported in gnomAD v4.1 (AN 1,605,720) (gnomAD).

How is PMM2-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PMM2 p.Pro20=

c.60G>A · rs2141014167 · VCV1158303

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,605,720)

Conditions

PMM2-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 0.81, phastCons 1
Overall
CADD	12.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,605,720). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PMM2
Protein: p.Pro20=
Coding: c.60G>A
MANE Select: NM_000303
dbSNP: rs2141014167
Type: single nucleotide variant
Location: chr16:8797942 (GRCh38)
Gene constraint: LOEUF 1.937 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.66 · 7 PDB
Residue 20: a UniProt-annotated variant site (in cdg1a; reduction of activity)

Full PMM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PMM2-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For PMM2-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Italy)

Similar variants

PMM2 p.Pro20Leu Uncertain significance ★★ ⚠ same residue
PMM2 p.Pro20Arg Uncertain significance ★ ⚠ same residue
PMM2 p.Pro20Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
PMM2 p.Pro20fs Pathogenic ★ same residue
PMM2 c.178+1G>A Likely pathogenic ★★ same condition
PMM2 c.178+2T>G Likely pathogenic ★★ same condition
PMM2 c.179-1G>C Pathogenic/Likely pathogenic ★★ same condition
PMM2 c.179-25A>G Likely pathogenic ★★ same condition

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/pmm2-p-pro20 (accessed [today's date]).

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