Is TOPORS p.Ser773= (c.2319T>C) pathogenic?

TOPORS p.Ser773= (c.2319T>C) is classified Benign in TOPORS (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Common (popmax 36.3%, sas) — too common for a highly-penetrant pathogenic allele; Associated with inherited retinal dystrophy.

What condition is associated with TOPORS p.Ser773= (c.2319T>C)?

TOPORS p.Ser773= (c.2319T>C) is associated with inherited retinal dystrophy, retinitis pigmentosa 31, retinitis pigmentosa (ClinVar).

TOPORS p.Ser773=

Q: How common is TOPORS p.Ser773= (c.2319T>C) in the general population?

TOPORS p.Ser773= (c.2319T>C) is common (popmax 36.3%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2319T>C · rs10971019 · VCV95313

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 36.3%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

inherited retinal dystrophy

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 0.17	GERP -4.5, phastCons 0.31
Overall
CADD	3.265	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 36.3% South Asian · 33,099/91,070 alleles

Filtering AF 36% ClinGen BA1/BS1 input FAF95, joint · FAF99 35.9%

Overall 21.6% 349,430/1,614,016 alleles · common exomes 322,679/1,461,854 · genomes 26,751/152,162 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	36.3%	3
Amishnot grpmax-eligible	26.4%	4
Middle Eastern	23.7%	4
Ashkenazi Jewishnot grpmax-eligible	23.2%	4
European (non-Finnish)	22.3%	4
Remaining individualsnot grpmax-eligible	21.1%	5
Admixed American	17.9%	6
Finnishnot grpmax-eligible	15.8%	6
African / African-American	8.49%	12
East Asian	8.22%	12

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: TOPORS
Protein: p.Ser773=
Coding: c.2319T>C
MANE Select: NM_005802
dbSNP: rs10971019
Type: single nucleotide variant
Location: chr9:32542206 (GRCh38)
Gene constraint: LOEUF 0.418 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 49.39
Residue 773: the 'disordered' region; the 'interaction with top1' region

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 31 retinitis pigmentosa

Similar variants

TOPORS p.Ser773Cys Uncertain significance ★ ⚠ same residue
TOPORS p.Arg847Ter Pathogenic/Likely pathogenic ★★ same condition
TOPORS p.Glu808Ter Pathogenic ★★ same condition
TOPORS c.*300A>G Uncertain significance ★★ same condition
TOPORS p.Ala190Thr Uncertain significance ★★ ⚠ same condition
TOPORS p.Arg598Thr Uncertain significance ★★ ⚠ same condition
TOPORS p.Arg683Gln Uncertain significance ★★ ⚠ same condition
TOPORS p.Arg721Gly 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/topors-p-ser773 (accessed [today's date]).

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