Is NOVA2 p.Ala390Val (c.1169C>T) pathogenic?

NOVA2 p.Ala390Val (c.1169C>T) is classified Uncertain significance in NOVA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-05). AlphaMissense: likely benign (0.1527); Very rare (popmax 8.51e-05%, nfe).

How common is NOVA2 p.Ala390Val (c.1169C>T) in the general population?

NOVA2 p.Ala390Val (c.1169C>T) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

What do computational predictors say about NOVA2 p.Ala390Val (c.1169C>T)?

AlphaMissense predicts likely benign (score 0.1527) — an in-silico prediction, not a clinical call.

NOVA2 p.Ala390Val

c.1169C>T · VCV4883636

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1527 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1527	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -8.64	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 33 kb · p 1.6e-21 · regional, not allelic
Overall
CADD	21.5	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 8.51e-05% European (non-Finnish) · 1/1,174,560 alleles

Overall 6.28e-05% 1/1,592,064 alleles · very rare exomes 1/1,441,832 · genomes 0/150,232 · 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.Ala390Val
Coding: c.1169C>T
MANE Select: NM_002516
Type: single nucleotide variant
Location: chr19:45940173 (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

Similar variants

NOVA2 p.Ala247Thr Uncertain significance ★★ ⚠ same type
NOVA2 p.Ala287= Benign ★★ same type
NOVA2 p.Ala383= Benign/Likely benign ★★ same type
NOVA2 p.Asn292Thr Likely benign ★★ same type
NOVA2 p.Ile39= Benign/Likely benign ★★ same type
NOVA2 p.Leu135= Likely benign ★★ same type
NOVA2 p.Leu238= Benign ★★ same type
NOVA2 p.Pro127= Likely benign ★★ same type

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-ala390val (accessed [today's date]).

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