Is NOVA2 p.Pro239Gln (c.716C>A) pathogenic?

NOVA2 p.Pro239Gln (c.716C>A) is classified Uncertain significance in NOVA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-11). AlphaMissense: ambiguous (0.4256); No allele count reported in gnomAD v4.1 (AN 1,472,538); Associated with Inborn genetic diseases.

What condition is associated with NOVA2 p.Pro239Gln (c.716C>A)?

NOVA2 p.Pro239Gln (c.716C>A) is associated with Inborn genetic diseases (ClinVar).

How common is NOVA2 p.Pro239Gln (c.716C>A) in the general population?

NOVA2 p.Pro239Gln (c.716C>A) is no allele count reported in gnomAD v4.1 (AN 1,472,538) (gnomAD).

What do computational predictors say about NOVA2 p.Pro239Gln (c.716C>A)?

AlphaMissense predicts ambiguous (score 0.4256) — an in-silico prediction, not a clinical call.

NOVA2 p.Pro239Gln

c.716C>A · rs1161675557 · VCV2394371

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4256 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,472,538)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4256	ambiguous
REVEL	0.095	moderately benign-leaning
SaProt	LLR -5.89	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
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	22.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,472,538). 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: NOVA2
Protein: p.Pro239Gln
Coding: c.716C>A
MANE Select: NM_002516
dbSNP: rs1161675557
Type: single nucleotide variant
Location: chr19:45940626 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NOVA2 p.Pro239Ala Uncertain significance ★ ⚠ same residue
NOVA2 p.Ala247Thr Uncertain significance ★★ ⚠ same condition
NOVA2 p.Asn292Thr Likely benign ★★ same condition
NOVA2 p.Ala240Thr Uncertain significance ★ ⚠ same condition
NOVA2 p.Ala248Pro Uncertain significance ★ ⚠ same condition
NOVA2 p.Ala331Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
NOVA2 p.Ala334Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
NOVA2 p.Ala339Pro 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-pro239gln (accessed [today's date]).

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