Is PMM2 p.Asp30= (c.90C>T) pathogenic?

PMM2 p.Asp30= (c.90C>T) is classified Likely benign in PMM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-13). Very rare (popmax 0.0011%, sas); Associated with PMM2-congenital disorder of glycosylation.

What condition is associated with PMM2 p.Asp30= (c.90C>T)?

PMM2 p.Asp30= (c.90C>T) is associated with PMM2-congenital disorder of glycosylation (ClinVar).

How common is PMM2 p.Asp30= (c.90C>T) in the general population?

PMM2 p.Asp30= (c.90C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

How is PMM2-CDG inherited?

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

PMM2 p.Asp30=

c.90C>T · VCV3611878

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 2.6	GERP 0.1, phastCons 0.99
Overall
CADD	10.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,786 alleles

Overall 6.21e-05% 1/1,610,108 alleles · very rare exomes 1/1,457,850 · genomes 0/152,258 · joint denominator

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: PMM2
Protein: p.Asp30=
Coding: c.90C>T
MANE Select: NM_000303
Type: single nucleotide variant
Location: chr16:8801822 (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 30: an α-helix

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.Asp30Glu Conflicting classifications of pathogenicity ★ ⚠ 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
PMM2 c.255+1G>A Pathogenic/Likely pathogenic ★★ same condition
PMM2 c.255+2T>C Pathogenic/Likely pathogenic ★★ same condition
PMM2 c.256-1G>C 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-asp30 (accessed [today's date]).

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