Is MPV17 p.Arg41fs (c.122_147del) pathogenic?

MPV17 p.Arg41fs (c.122147del) is classified Pathogenic in MPV17 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2006-05-01). No gnomAD frequency available for this variant; Associated with mitochondrial DNA depletion syndrome 6 (hepatocerebral type).

What condition is associated with MPV17 p.Arg41fs (c.122_147del)?

MPV17 p.Arg41fs (c.122_147del) is associated with mitochondrial DNA depletion syndrome 6 (hepatocerebral type) (ClinVar).

How common is MPV17 p.Arg41fs (c.122_147del) in the general population?

MPV17 p.Arg41fs (c.122_147del) is no gnomAD frequency available for this variant (gnomAD).

How is Navajo neurohepatopathy inherited?

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

MPV17 p.Arg41fs

c.122_147del · rs397507438 · VCV16163

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 3 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.2	GERP 1.9, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MPV17
Protein: p.Arg41fs
Coding: c.122_147del
MANE Select: NM_002437
dbSNP: rs397507438
Type: Deletion
Location: chr2:27313033 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.23
Residue 41: a UniProt-annotated variant site (in cmt2ee); a UniProt-annotated variant site (in mtdps6)

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.Arg41Gln Pathogenic/Likely pathogenic ★★ ⚠ same residue
MPV17 p.Arg41Trp Conflicting classifications of pathogenicity ★ ⚠ 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.Pro98fs Pathogenic ★★ same condition
MPV17 p.Val38fs Pathogenic ★ same condition
MPV17 p.Gly79_Thr81del Conflicting classifications of pathogenicity ★ 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/mpv17-p-arg41fs (accessed [today's date]).

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