Is TOP1 p.Ile482= (c.1446C>T) pathogenic?

TOP1 p.Ile482= (c.1446C>T) is classified Likely benign in TOP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-09). Ultra-rare (popmax 0.0879%, afr); Associated with TOP1-related disorder.

What condition is associated with TOP1 p.Ile482= (c.1446C>T)?

TOP1 p.Ile482= (c.1446C>T) is associated with TOP1-related disorder (ClinVar).

How common is TOP1 p.Ile482= (c.1446C>T) in the general population?

TOP1 p.Ile482= (c.1446C>T) is ultra-rare (popmax 0.0879%, afr) (gnomAD).

TOP1 p.Ile482=

c.1446C>T · rs147984700 · VCV3046725

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0879%, afr)

Conditions

TOP1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.5	GERP -3.7
Overall
CADD	6.395	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0879% African / African-American · 66/75,068 alleles

Filtering AF 0.0709% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0647%

Overall 0.00514% 83/1,613,888 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0879%	1,137
Remaining individualsnot grpmax-eligible	0.0128%	7,812
Admixed American	0.00667%	14,997
European (non-Finnish)	0.000424%	235,967

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: TOP1
Protein: p.Ile482=
Coding: c.1446C>T
dbSNP: rs147984700
Type: single nucleotide variant
Location: chr20:41112919 (GRCh38)

Full TOP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

TOP1-related disorder

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/top1-p-ile482 (accessed [today's date]).

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