Is POLRMT p.Pro734fs (c.2201_2205del) pathogenic?

POLRMT p.Pro734fs (c.22012205del) is classified Pathogenic in POLRMT (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-30). Associated with combined oxidative phosphorylation deficiency 55.

What condition is associated with POLRMT p.Pro734fs (c.2201_2205del)?

POLRMT p.Pro734fs (c.2201_2205del) is associated with combined oxidative phosphorylation deficiency 55 (ClinVar).

POLRMT p.Pro734fs

c.2201_2205del · VCV4879669

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

combined oxidative phosphorylation deficiency 55

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 10 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5	GERP -0.17, phastCons 1

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

Variant & gene context

Gene: POLRMT
Protein: p.Pro734fs
Coding: c.2201_2205del
MANE Select: NM_005035
Type: Deletion
Location: chr19:621493 (GRCh38)
Gene constraint: LOEUF 1.26 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.99 · 25 PDB
Residue 734: a UniProt-annotated variant site (in coxpd55); the 'disordered' region; an α-helix

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

Disease context

combined oxidative phosphorylation deficiency 55 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

POLRMT p.Leu714fs Likely pathogenic ★ same condition
POLRMT p.Leu833_Pro835del Uncertain significance ★ same condition
POLRMT p.Pro742_Pro747del Conflicting classifications of pathogenicity ★ same condition
POLRMT p.Gln681Ter Pathogenic/Likely pathogenic ★★ same condition
POLRMT p.Ala409Val Uncertain significance ★★ ⚠ same condition
POLRMT p.Ala444Val Uncertain significance ★★ ⚠ same condition
POLRMT p.Arg447Gln Uncertain significance ★★ ⚠ same condition
POLRMT p.Gly711Arg 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/polrmt-p-pro734fs (accessed [today's date]).

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