Is MPI p.Val342fs (c.1022dup) pathogenic?

MPI p.Val342fs (c.1022dup) is classified Pathogenic/Likely pathogenic in MPI (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-10). Very rare (popmax 0.00402%, afr); Associated with MPI-congenital disorder of glycosylation.

What condition is associated with MPI p.Val342fs (c.1022dup)?

MPI p.Val342fs (c.1022dup) is associated with MPI-congenital disorder of glycosylation (ClinVar).

How common is MPI p.Val342fs (c.1022dup) in the general population?

MPI p.Val342fs (c.1022dup) is very rare (popmax 0.00402%, afr) (gnomAD).

How is MPI-CDG inherited?

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

MPI p.Val342fs

c.1022dup · rs765310894 · VCV1368178

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00402%, afr)

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (7 of 8, 37 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.9	GERP 0.19, phastCons 0.98
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00402% African / African-American · 3/74,710 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000496%

Overall 0.000372% 6/1,613,432 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00402%	24,903
Admixed American	0.00167%	59,928
South Asian	0.0011%	91,042
European (non-Finnish)	8.48e-05%	1,179,915

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.Val342fs
Coding: c.1022dup
MANE Select: NM_002435
dbSNP: rs765310894
Type: Duplication
Location: chr15:74897182 (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.Arg56fs Pathogenic ★★ same condition
MPI p.Leu335fs Pathogenic/Likely pathogenic ★★ same condition
MPI p.Lys115Ter Pathogenic/Likely pathogenic ★★ same condition
MPI p.Gln124fs Pathogenic ★ same condition
MPI p.Glu236fs Pathogenic ★ same condition
MPI p.Gly265fs Pathogenic ★ same condition
MPI p.His178fs Likely pathogenic ★ same condition
MPI p.Ile249fs 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-val342fs (accessed [today's date]).

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