Is TOPORS p.Pro174= (c.522T>C) pathogenic?

TOPORS p.Pro174= (c.522T>C) is classified Likely benign in TOPORS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-23). Absent from gnomAD v4.1.

How common is TOPORS p.Pro174= (c.522T>C) in the general population?

TOPORS p.Pro174= (c.522T>C) is absent from gnomAD v4.1 (gnomAD).

TOPORS p.Pro174=

c.522T>C · VCV4902948

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.037	GERP -1.9, phastCons 0.038
Overall
CADD	7.561	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: TOPORS
Protein: p.Pro174=
Coding: c.522T>C
MANE Select: NM_005802
Type: single nucleotide variant
Location: chr9:32544003 (GRCh38)
Gene constraint: LOEUF 0.418 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 49.39
Residue 174: the 'e3 ubiquitin-protein ligase activity' region; the 'required for dna-binding' region

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

Similar variants

TOPORS p.Arg847Ter Pathogenic/Likely pathogenic ★★ same type
TOPORS p.Gln811Ter Likely pathogenic ★★ same type
TOPORS p.Glu808Ter Pathogenic ★★ same type
TOPORS c.*300A>G Uncertain significance ★★ same type
TOPORS p.Ala154Ser Uncertain significance ★★ ⚠ same type
TOPORS p.Ala190Thr Uncertain significance ★★ ⚠ same type
TOPORS p.Ala399Asp Uncertain significance ★★ ⚠ same type
TOPORS p.Ala56Ser Uncertain significance ★★ ⚠ same type

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/topors-p-pro174 (accessed [today's date]).

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