Is PMM2 p.Phe122= (c.366C>T) pathogenic?

PMM2 p.Phe122= (c.366C>T) is classified Benign/Likely benign in PMM2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-02). Rare (popmax 0.669%, eas); Associated with PMM2-congenital disorder of glycosylation.

What condition is associated with PMM2 p.Phe122= (c.366C>T)?

PMM2 p.Phe122= (c.366C>T) is associated with PMM2-congenital disorder of glycosylation (ClinVar).

How common is PMM2 p.Phe122= (c.366C>T) in the general population?

PMM2 p.Phe122= (c.366C>T) is rare (popmax 0.669%, eas) (gnomAD).

How is PMM2-CDG inherited?

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

PMM2 p.Phe122=

c.366C>T · rs145714866 · VCV281078

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.669%, eas)

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 3.2	GERP 1.1, phastCons 1
Overall
CADD	14.14	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.669% East Asian · 288/43,048 alleles

Filtering AF 0.605% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.581%

Overall 0.0405% 636/1,569,762 alleles · rare exomes 583/1,417,498 · genomes 53/152,264 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.669%	149
Remaining individualsnot grpmax-eligible	0.237%	421
South Asian	0.022%	4,544
European (non-Finnish)	0.0153%	6,554
Admixed American	0.0144%	6,931
African / African-American	0.00135%	73,958

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.Phe122=
Coding: c.366C>T
MANE Select: NM_000303
dbSNP: rs145714866
Type: single nucleotide variant
Location: chr16:8811097 (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 122: a β-strand

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.Phe122Leu Uncertain significance ★ ⚠ 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-phe122 (accessed [today's date]).

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