Is MGAT2 p.Pro77Ser (c.229C>T) pathogenic?

MGAT2 p.Pro77Ser (c.229C>T) is classified Conflicting classifications of pathogenicity in MGAT2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-18). AlphaMissense: likely benign (0.0735); Rare (popmax 0.706%, afr); Associated with MGAT2-congenital disorder of glycosylation.

What condition is associated with MGAT2 p.Pro77Ser (c.229C>T)?

MGAT2 p.Pro77Ser (c.229C>T) is associated with MGAT2-congenital disorder of glycosylation (ClinVar).

How common is MGAT2 p.Pro77Ser (c.229C>T) in the general population?

MGAT2 p.Pro77Ser (c.229C>T) is rare (popmax 0.706%, afr) (gnomAD).

How is MGAT2-CDG inherited?

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

What do computational predictors say about MGAT2 p.Pro77Ser (c.229C>T)?

AlphaMissense predicts likely benign (score 0.0735) — an in-silico prediction, not a clinical call.

MGAT2 p.Pro77Ser

c.229C>T · rs145684106 · VCV702828

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0735 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.706%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MGAT2-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0735	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.59	GERP -1.4, phastCons 0.29
Overall
CADD	9.931	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.706% African / African-American · 530/75,022 alleles

Filtering AF 0.657% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.637%

Overall 0.036% 580/1,610,912 alleles · rare exomes 299/1,458,582 · genomes 281/152,330 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.706%	142
Admixed American	0.04%	2,499
Remaining individualsnot grpmax-eligible	0.0353%	2,834
Middle Eastern	0.0165%	6,052
South Asian	0.0011%	91,052
European (non-Finnish)	0.00017%	589,136

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.Pro77Ser
Coding: c.229C>T
MANE Select: NM_002408
dbSNP: rs145684106
Type: single nucleotide variant
Location: chr14:49621497 (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.Pro77Leu Uncertain significance ★ ⚠ same residue
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

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-pro77ser (accessed [today's date]).

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