Is NOVA2 p.Ser404fs (c.1210_1211del) pathogenic?

NOVA2 p.Ser404fs (c.12101211del) is classified Uncertain significance in NOVA2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-05). Associated with NOVA2-related disorder.

What condition is associated with NOVA2 p.Ser404fs (c.1210_1211del)?

NOVA2 p.Ser404fs (c.1210_1211del) is associated with NOVA2-related disorder (ClinVar).

NOVA2 p.Ser404fs

c.1210_1211del · VCV3346967

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

NOVA2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.6	GERP -5.3

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

Variant & gene context

Gene: NOVA2
Protein: p.Ser404fs
Coding: c.1210_1211del
MANE Select: NM_002516
Type: Microsatellite
Location: chr19:45940131 (GRCh38)
Gene constraint: LOEUF 0.611 · pLI 0.85 (gnomAD)
Structure: AlphaFold pLDDT 65.60 · 2 PDB

Full NOVA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

NOVA2-related disorder

Similar variants

NOVA2 p.Ser404Asn Uncertain significance ★ ⚠ same residue
NOVA2 p.Ala324del Likely benign same condition
NOVA2 p.Gly369fs Likely pathogenic ★ same condition
NOVA2 p.Leu276fs Likely pathogenic ★ same condition
NOVA2 p.Val237Ala Uncertain significance ★ ⚠ same condition
NOVA2 p.Ala384= Likely benign same condition
NOVA2 p.Ala385= Likely benign same condition
NOVA2 p.Ala386= Likely 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/nova2-p-ser404fs (accessed [today's date]).

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