Is PMPCB p.Arg481fs (c.1440dup) pathogenic?

PMPCB p.Arg481fs (c.1440dup) is classified Likely pathogenic in PMPCB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-29). Associated with multiple mitochondrial dysfunctions syndrome 6.

What condition is associated with PMPCB p.Arg481fs (c.1440dup)?

PMPCB p.Arg481fs (c.1440dup) is associated with multiple mitochondrial dysfunctions syndrome 6 (ClinVar).

PMPCB p.Arg481fs

Q: How is Multiple mitochondrial dysfunctions syndrome type 6 inherited?

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

c.1440dup · VCV4886879

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

multiple mitochondrial dysfunctions syndrome 6

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 in the last exon (13 of 13) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.2	GERP 1.7, phastCons 1

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

Variant & gene context

Gene: PMPCB
Protein: p.Arg481fs
Coding: c.1440dup
MANE Select: NM_004279
Type: Duplication
Location: chr7:103312240 (GRCh38)
Gene constraint: LOEUF 1.085 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.48

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

Disease context

multiple mitochondrial dysfunctions syndrome 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Multiple mitochondrial dysfunctions syndrome type 6 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

PMPCB p.Thr360fs Likely pathogenic ★ same condition
PMPCB p.Arg481Cys Uncertain significance ★ ⚠ same residue
PMPCB p.Arg175Cys Likely pathogenic ★★ same condition
PMPCB p.Gln46Lys Uncertain significance ★★ ⚠ same condition
PMPCB p.Ile221Val Uncertain significance ★★ ⚠ same condition
PMPCB p.Leu119Met Uncertain significance ★★ ⚠ same condition
PMPCB p.Leu157Arg Uncertain significance ★★ ⚠ same condition
PMPCB p.Leu378Gln Uncertain significance ★★ 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/pmpcb-p-arg481fs (accessed [today's date]).

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