Is MPI p.Ser204Arg (c.612T>G) pathogenic?

MPI p.Ser204Arg (c.612T>G) is classified Uncertain significance in MPI (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-21). AlphaMissense: ambiguous (0.3489); Absent from gnomAD v4.1; Associated with MPI-congenital disorder of glycosylation.

What condition is associated with MPI p.Ser204Arg (c.612T>G)?

MPI p.Ser204Arg (c.612T>G) is associated with MPI-congenital disorder of glycosylation (ClinVar).

How common is MPI p.Ser204Arg (c.612T>G) in the general population?

MPI p.Ser204Arg (c.612T>G) is absent from gnomAD v4.1 (gnomAD).

How is MPI-CDG inherited?

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

What do computational predictors say about MPI p.Ser204Arg (c.612T>G)?

AlphaMissense predicts ambiguous (score 0.3489) — an in-silico prediction, not a clinical call.

MPI p.Ser204Arg

c.612T>G · rs886043207 · VCV285772

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3489 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

MPI-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.3489	ambiguous
REVEL	0.481	indeterminate
SaProt	LLR -6.67	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.3	GERP -4.6
Regional constraint	o/e 0.98	unconstrained · MANE · 7,653 bp · p 0.66 · regional, not allelic
Overall
CADD	0.135	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MPI
Protein: p.Ser204Arg
Coding: c.612T>G
MANE Select: NM_002435
dbSNP: rs886043207
Type: single nucleotide variant
Location: chr15:74893262 (GRCh38)
Gene constraint: LOEUF 1.04 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.50

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

Disease context

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

For MPI-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

MPI p.Ser204fs Pathogenic ★ same residue
MPI c.145-1G>C Likely pathogenic ★★ same condition
MPI c.16+2T>C Likely pathogenic ★★ same condition
MPI c.488-1G>C Pathogenic/Likely pathogenic ★★ same condition
MPI c.488-2A>G Likely pathogenic ★★ same condition
MPI c.844+1G>A Likely pathogenic ★★ same condition
MPI c.845-2A>G Likely pathogenic ★★ same condition
MPI p.Arg219Gln 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/mpi-p-ser204arg (accessed [today's date]).

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