Is MGAT2 p.Phe22= (c.66C>T) pathogenic?

MGAT2 p.Phe22= (c.66C>T) is classified Uncertain significance in MGAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Very rare (popmax 0.00534%, afr); Associated with MGAT2-congenital disorder of glycosylation.

What condition is associated with MGAT2 p.Phe22= (c.66C>T)?

MGAT2 p.Phe22= (c.66C>T) is associated with MGAT2-congenital disorder of glycosylation (ClinVar).

How common is MGAT2 p.Phe22= (c.66C>T) in the general population?

MGAT2 p.Phe22= (c.66C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

How is MGAT2-CDG inherited?

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

MGAT2 p.Phe22=

c.66C>T · rs758108747 · VCV884090

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

MGAT2-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 1.7	GERP 1.9, phastCons 1
Overall
CADD	18.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,926 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00062% 10/1,612,452 alleles · very rare exomes 5/1,460,188 · genomes 5/152,264 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,732
European (non-Finnish)	0.000509%	196,633

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: MGAT2
Protein: p.Phe22=
Coding: c.66C>T
MANE Select: NM_002408
dbSNP: rs758108747
Type: single nucleotide variant
Location: chr14:49621334 (GRCh38)
Structure: AlphaFold pLDDT 94.86

Full MGAT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MGAT2-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For MGAT2-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

MGAT2 p.Lys237Asn Likely pathogenic ★★ same condition
MGAT2 p.Ala421Val Uncertain significance ★★ ⚠ same condition
MGAT2 p.Ala78Thr Uncertain significance ★★ ⚠ same condition
MGAT2 p.Asn146Ser Uncertain significance ★★ ⚠ same condition
MGAT2 p.Asn186Lys Uncertain significance ★★ ⚠ same condition
MGAT2 p.Gln182Glu Uncertain significance ★★ ⚠ same condition
MGAT2 p.Gln281Pro Uncertain significance ★★ ⚠ same condition
MGAT2 p.Gly49Asp Uncertain significance ★★ ⚠ 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/mgat2-p-phe22 (accessed [today's date]).

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