Is NOVA2 p.Ala247Thr (c.739G>A) pathogenic?

NOVA2 p.Ala247Thr (c.739G>A) is classified Uncertain significance in NOVA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-06-27). AlphaMissense: likely benign (0.1026); No allele count reported in gnomAD v4.1 (AN 1,420,632); Associated with Inborn genetic diseases.

What condition is associated with NOVA2 p.Ala247Thr (c.739G>A)?

NOVA2 p.Ala247Thr (c.739G>A) is associated with Inborn genetic diseases (ClinVar).

How common is NOVA2 p.Ala247Thr (c.739G>A) in the general population?

NOVA2 p.Ala247Thr (c.739G>A) is no allele count reported in gnomAD v4.1 (AN 1,420,632) (gnomAD).

What do computational predictors say about NOVA2 p.Ala247Thr (c.739G>A)?

AlphaMissense predicts likely benign (score 0.1026) — an in-silico prediction, not a clinical call.

NOVA2 p.Ala247Thr

c.739G>A · rs765194093 · VCV1686725

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1026 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,420,632)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1026	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -10.22	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 2.1, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 33 kb · p 1.6e-21 · regional, not allelic
Overall
CADD	21.9	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 1,420,632). 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.Ala247Thr
Coding: c.739G>A
MANE Select: NM_002516
dbSNP: rs765194093
Type: single nucleotide variant
Location: chr19:45940603 (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.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
NOVA2 p.Ala362Thr Uncertain significance ★ ⚠ same condition
NOVA2 p.Ala374Gly 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-ala247thr (accessed [today's date]).

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