Is MPV17 p.Ala97= (c.291C>T) pathogenic?

MPV17 p.Ala97= (c.291C>T) is classified Uncertain significance in MPV17 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Absent from gnomAD v4.1; Associated with mitochondrial DNA depletion syndrome 6 (hepatocerebral type).

What condition is associated with MPV17 p.Ala97= (c.291C>T)?

MPV17 p.Ala97= (c.291C>T) is associated with mitochondrial DNA depletion syndrome 6 (hepatocerebral type) (ClinVar).

How common is MPV17 p.Ala97= (c.291C>T) in the general population?

MPV17 p.Ala97= (c.291C>T) is absent from gnomAD v4.1 (gnomAD).

How is Navajo neurohepatopathy inherited?

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

MPV17 p.Ala97=

c.291C>T · rs1679491926 · VCV898499

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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.
REVEL	0.468	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 0.38, phastCons 1
Overall
CADD	10.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MPV17
Protein: p.Ala97=
Coding: c.291C>T
MANE Select: NM_002437
dbSNP: rs1679491926
Type: single nucleotide variant
Location: chr2:27312578 (GRCh38)
Gene constraint: LOEUF 1.368 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.23
Residue 97: 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 c.186+2T>C Pathogenic/Likely pathogenic ★★ same condition
MPV17 c.279+1G>T Pathogenic ★★ same condition
MPV17 c.375+1G>A Likely pathogenic ★★ same condition
MPV17 c.375+1G>T Likely pathogenic ★★ same condition
MPV17 c.376-1G>A Pathogenic/Likely pathogenic ★★ same condition
MPV17 c.376-2A>C Pathogenic/Likely pathogenic ★★ same condition
MPV17 c.408+1G>A Pathogenic/Likely pathogenic ★★ same condition
MPV17 c.461+1G>C 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/mpv17-p-ala97 (accessed [today's date]).

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