Is MPI p.Ser72Arg (c.214A>C) pathogenic?

MPI p.Ser72Arg (c.214A>C) is classified Benign/Likely benign in MPI (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.2845); Low-frequency (popmax 1.74%, eas); Associated with MPI-congenital disorder of glycosylation.

What condition is associated with MPI p.Ser72Arg (c.214A>C)?

MPI p.Ser72Arg (c.214A>C) is associated with MPI-congenital disorder of glycosylation (ClinVar).

How common is MPI p.Ser72Arg (c.214A>C) in the general population?

MPI p.Ser72Arg (c.214A>C) is low-frequency (popmax 1.74%, eas) (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.Ser72Arg (c.214A>C)?

AlphaMissense predicts likely benign (score 0.2845) — an in-silico prediction, not a clinical call.

MPI p.Ser72Arg

c.214A>C · rs146699267 · VCV585033

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.2845 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.74%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

MPI-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.2845	likely benign
REVEL	0.46	indeterminate
SaProt	LLR -6.63	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP -1.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 7,653 bp · p 0.66 · regional, not allelic
Overall
CADD	21.4	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 1.74% East Asian · 783/44,892 alleles

Filtering AF 1.64% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.6%

Overall 0.0537% 867/1,614,230 alleles · low-frequency exomes 787/1,461,894 · genomes 80/152,336 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.74%	57
Remaining individualsnot grpmax-eligible	0.0848%	1,179
African / African-American	0.02%	5,004
South Asian	0.0132%	7,591
Admixed American	0.00333%	30,011
European (non-Finnish)	0.000169%	590,023

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: MPI
Protein: p.Ser72Arg
Coding: c.214A>C
MANE Select: NM_002435
dbSNP: rs146699267
Type: single nucleotide variant
Location: chr15:74891448 (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.Ser72= Likely benign ★★ 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-ser72arg (accessed [today's date]).

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