Is MPI p.Phe324fs (c.969_970del) pathogenic?

MPI p.Phe324fs (c.969970del) is classified Pathogenic/Likely pathogenic in MPI (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-18). Very rare (popmax 0.00333%, amr); Associated with MPI-congenital disorder of glycosylation.

What condition is associated with MPI p.Phe324fs (c.969_970del)?

MPI p.Phe324fs (c.969_970del) is associated with MPI-congenital disorder of glycosylation (ClinVar).

How common is MPI p.Phe324fs (c.969_970del) in the general population?

MPI p.Phe324fs (c.969_970del) is very rare (popmax 0.00333%, amr) (gnomAD).

How is MPI-CDG inherited?

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

MPI p.Phe324fs

c.969_970del · rs1276918786 · VCV2154686

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

MPI-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5	GERP 1.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,018 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000372% 6/1,614,182 alleles · very rare exomes 6/1,461,886 · genomes 0/152,296 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,009
European (non-Finnish)	0.000339%	295,006

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.Phe324fs
Coding: c.969_970del
MANE Select: NM_002435
dbSNP: rs1276918786
Type: Microsatellite
Location: chr15:74897133 (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.Ser355fs Pathogenic/Likely pathogenic ★★ same condition
MPI p.Leu194fs Likely pathogenic ★ same condition
MPI p.Ser336fs Pathogenic ★ same condition
MPI p.Ser403fs Likely pathogenic ★ same condition
MPI p.Thr293fs Likely pathogenic ★ same condition
MPI c.843_844+1del Conflicting classifications of pathogenicity ★ same condition
MPI c.670+8_670+9del Likely benign ★ same condition
MPI c.671-13_671-12del Likely benign ★ 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-phe324fs (accessed [today's date]).

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