Is PMM2 p.Phe183= (c.549T>C) pathogenic?

PMM2 p.Phe183= (c.549T>C) is classified Likely benign in PMM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-24). Very rare (popmax 0.00221%, nfe); Associated with PMM2-congenital disorder of glycosylation.

What condition is associated with PMM2 p.Phe183= (c.549T>C)?

PMM2 p.Phe183= (c.549T>C) is associated with PMM2-congenital disorder of glycosylation (ClinVar).

How common is PMM2 p.Phe183= (c.549T>C) in the general population?

PMM2 p.Phe183= (c.549T>C) is very rare (popmax 0.00221%, nfe) (gnomAD).

How is PMM2-CDG inherited?

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

PMM2 p.Phe183=

c.549T>C · rs1426754260 · VCV1092751

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00221%, nfe)

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 0.091	GERP -4.2, phastCons 0.98
Overall
CADD	7.702	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00221% European (non-Finnish) · 26/1,178,970 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00161% 26/1,612,966 alleles · very rare exomes 24/1,460,734 · genomes 2/152,232 · 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.Phe183=
Coding: c.549T>C
MANE Select: NM_000303
dbSNP: rs1426754260
Type: single nucleotide variant
Location: chr16:8813016 (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 183: a β-strand; a UniProt-annotated variant site (in cdg1a)

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.Phe183Ser Pathogenic ★★ same residue
PMM2 p.Phe183Leu Likely 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
PMM2 c.255+1G>A Pathogenic/Likely pathogenic ★★ same condition
PMM2 c.255+2T>C Pathogenic/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-phe183 (accessed [today's date]).

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