Is PRORP p.Arg502fs (c.1504dup) pathogenic?

PRORP p.Arg502fs (c.1504dup) is classified Likely pathogenic in PRORP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-16). Associated with combined oxidative phosphorylation deficiency 54.

What condition is associated with PRORP p.Arg502fs (c.1504dup)?

PRORP p.Arg502fs (c.1504dup) is associated with combined oxidative phosphorylation deficiency 54 (ClinVar).

PRORP p.Arg502fs

c.1504dup · VCV4849383

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

combined oxidative phosphorylation deficiency 54

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 7 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.8	GERP 1.2, phastCons 1

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

Variant & gene context

Gene: PRORP
Protein: p.Arg502fs
Coding: c.1504dup
MANE Select: NM_014672
Type: Duplication
Location: chr14:35270479 (GRCh38)
Gene constraint: LOEUF 0.999 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.19 · 5 PDB
Residue 502: the prorp domain; an α-helix

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

Disease context

combined oxidative phosphorylation deficiency 54 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRORP p.Arg502Gln Uncertain significance ★★ ⚠ same residue
PRORP p.Ser400fs Pathogenic/Likely pathogenic same condition
PRORP p.Arg421Cys Uncertain significance ★★ ⚠ same condition
PRORP p.Asn412Ser Uncertain significance ★★ ⚠ same condition
PRORP p.Ala434Asp Likely pathogenic ★ ⚠ same condition
PRORP p.Gln312Ter Uncertain significance ★ same condition
PRORP p.Thr59fs Uncertain significance ★ same condition
PRORP p.Ala485Val Pathogenic/Likely 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/prorp-p-arg502fs (accessed [today's date]).

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