Is TOP3A p.Ser810fs (c.2428del) pathogenic?

TOP3A p.Ser810fs (c.2428del) is classified Pathogenic in TOP3A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-08-30). No gnomAD frequency available for this variant; Associated with microcephaly, growth restriction, and increased sister chromatid exchange 2.

What condition is associated with TOP3A p.Ser810fs (c.2428del)?

TOP3A p.Ser810fs (c.2428del) is associated with microcephaly, growth restriction, and increased sister chromatid exchange 2 (ClinVar).

How common is TOP3A p.Ser810fs (c.2428del) in the general population?

TOP3A p.Ser810fs (c.2428del) is no gnomAD frequency available for this variant (gnomAD).

TOP3A p.Ser810fs

c.2428del · rs1555568139 · VCV560204

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

microcephaly, growth restriction, and increased sister chromatid exchange 2

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 18 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.4	GERP 0.58, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TOP3A
Protein: p.Ser810fs
Coding: c.2428del
MANE Select: NM_004618
dbSNP: rs1555568139
Type: Deletion
Location: chr17:18278074 (GRCh38)
Gene constraint: LOEUF 0.737 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.14 · 2 PDB
Residue 810: a UniProt-annotated variant site (in peob5); the 'disordered' region

Full TOP3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

microcephaly, growth restriction, and increased sister chromatid exchange 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TOP3A p.Thr907fs Likely pathogenic ★ same condition
TOP3A p.Ser810= Likely benign ★ same residue
TOP3A p.Arg177Ter Pathogenic/Likely pathogenic ★★ same condition
TOP3A p.Arg758fs Pathogenic ★★ same condition
TOP3A p.Arg548Gln Uncertain significance ★★ ⚠ same condition
TOP3A p.Arg686Cys Uncertain significance ★★ ⚠ same condition
TOP3A p.Thr743Ser Uncertain significance ★★ ⚠ same condition
TOP3A c.1282-21G>A Benign ★★ 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/top3a-p-ser810fs (accessed [today's date]).

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