Is NOVA2 p.Val237Ala (c.710T>C) pathogenic?

NOVA2 p.Val237Ala (c.710T>C) is classified Uncertain significance in NOVA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-17). AlphaMissense: likely benign (0.1192); Very rare (popmax 8.86e-05%, nfe); Associated with NOVA2-related disorder.

What condition is associated with NOVA2 p.Val237Ala (c.710T>C)?

NOVA2 p.Val237Ala (c.710T>C) is associated with NOVA2-related disorder (ClinVar).

How common is NOVA2 p.Val237Ala (c.710T>C) in the general population?

NOVA2 p.Val237Ala (c.710T>C) is very rare (popmax 8.86e-05%, nfe) (gnomAD).

What do computational predictors say about NOVA2 p.Val237Ala (c.710T>C)?

AlphaMissense predicts likely benign (score 0.1192) — an in-silico prediction, not a clinical call.

NOVA2 p.Val237Ala

c.710T>C · rs2513852680 · VCV2630704

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1192 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.86e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

NOVA2-related disorder

Computational evidence

Protein change
AlphaMissense	0.1192	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -5.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 33 kb · p 1.6e-21 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.86e-05% European (non-Finnish) · 1/1,128,952 alleles

Overall 6.74e-05% 1/1,484,292 alleles · very rare exomes 1/1,332,104 · genomes 0/152,188 · joint denominator

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: NOVA2
Protein: p.Val237Ala
Coding: c.710T>C
MANE Select: NM_002516
dbSNP: rs2513852680
Type: single nucleotide variant
Location: chr19:45940632 (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.Val237fs Pathogenic same residue
NOVA2 p.Ala384= Likely benign same condition
NOVA2 p.Ala385= Likely benign same condition
NOVA2 p.Ala386= Likely benign same condition
NOVA2 p.Gly377= Likely benign same condition
NOVA2 p.Gly369fs Likely pathogenic ★ same condition
NOVA2 p.Leu276fs Likely pathogenic ★ same condition
NOVA2 p.Ser404fs 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/nova2-p-val237ala (accessed [today's date]).

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