Is MPV17 p.Pro98fs (c.293del) pathogenic?

MPV17 p.Pro98fs (c.293del) is classified Pathogenic in MPV17 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-04-03). Very rare (popmax 0.00167%, amr); Associated with mitochondrial DNA depletion syndrome 6 (hepatocerebral type).

What condition is associated with MPV17 p.Pro98fs (c.293del)?

MPV17 p.Pro98fs (c.293del) is associated with mitochondrial DNA depletion syndrome 6 (hepatocerebral type) (ClinVar).

How common is MPV17 p.Pro98fs (c.293del) in the general population?

MPV17 p.Pro98fs (c.293del) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Navajo neurohepatopathy inherited?

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

MPV17 p.Pro98fs

c.293del · rs1553383480 · VCV522374

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

mitochondrial DNA depletion syndrome 6 (hepatocerebral type)

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 5 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -13	GERP -5

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,020 alleles

Overall 6.2e-05% 1/1,614,098 alleles · very rare exomes 1/1,461,774 · genomes 0/152,324 · joint denominator

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: MPV17
Protein: p.Pro98fs
Coding: c.293del
MANE Select: NM_002437
dbSNP: rs1553383480
Type: Deletion
Location: chr2:27312576 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.23
Residue 98: a UniProt-annotated variant site (in mtdps6); a UniProt-annotated variant site (in mtdps6 and cmt2ee; results in incomplete closing of the channel)

Full MPV17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial DNA depletion syndrome 6 (hepatocerebral type) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Navajo neurohepatopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

MPV17 p.Pro98Leu Pathogenic/Likely pathogenic ★★ same residue
MPV17 p.Glu45fs Pathogenic/Likely pathogenic ★★ same condition
MPV17 p.Gly60fs Pathogenic/Likely pathogenic ★★ same condition
MPV17 p.Ile132fs Pathogenic/Likely pathogenic ★★ same condition
MPV17 p.Pro98Gln Likely pathogenic ★ same residue
MPV17 p.Val38fs Pathogenic ★ same condition
MPV17 p.Gly79_Thr81del Conflicting classifications of pathogenicity ★ same condition
MPV17 p.Pro98= Likely benign ★ same residue

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/mpv17-p-pro98fs (accessed [today's date]).

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