Is PRORP p.Gln312Ter (c.934C>T) pathogenic?

PRORP p.Gln312Ter (c.934C>T) is classified Uncertain significance in PRORP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-29). Very rare (popmax 8.52e-05%, nfe); Associated with combined oxidative phosphorylation deficiency 54.

What condition is associated with PRORP p.Gln312Ter (c.934C>T)?

PRORP p.Gln312Ter (c.934C>T) is associated with combined oxidative phosphorylation deficiency 54 (ClinVar).

How common is PRORP p.Gln312Ter (c.934C>T) in the general population?

PRORP p.Gln312Ter (c.934C>T) is very rare (popmax 8.52e-05%, nfe) (gnomAD).

PRORP p.Gln312Ter

c.934C>T · rs2503165684 · VCV3065718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.52e-05%, nfe)

Conditions

combined oxidative phosphorylation deficiency 54

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 8
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.7	GERP 1.2, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.52e-05% European (non-Finnish) · 1/1,173,864 alleles

Overall 6.25e-05% 1/1,599,272 alleles · very rare exomes 1/1,447,126 · genomes 0/152,146 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PRORP
Protein: p.Gln312Ter
Coding: c.934C>T
MANE Select: NM_014672
dbSNP: rs2503165684
Type: single nucleotide variant
Location: chr14:35124179 (GRCh38)
Gene constraint: LOEUF 0.999 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.19 · 5 PDB

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.Arg421Cys Uncertain significance ★★ ⚠ same condition
PRORP p.Arg502Gln Uncertain significance ★★ ⚠ same condition
PRORP p.Asn412Ser Uncertain significance ★★ ⚠ same condition
PRORP p.Ala434Asp Likely pathogenic ★ ⚠ same condition
PRORP p.Ala485Val Pathogenic/Likely pathogenic ⚠ same condition
PRORP p.Arg445Gln Pathogenic/Likely pathogenic same condition
PRORP p.His504Tyr Likely pathogenic same condition
PRORP p.Ser298Ter 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-gln312ter (accessed [today's date]).

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