Is NOVA2 p.Gly63Arg (c.187G>A) pathogenic?

NOVA2 p.Gly63Arg (c.187G>A) is classified Uncertain significance in NOVA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-27). AlphaMissense: likely pathogenic (0.8168); Ultra-rare (popmax 0.0147%, amr); Associated with Inborn genetic diseases.

What condition is associated with NOVA2 p.Gly63Arg (c.187G>A)?

NOVA2 p.Gly63Arg (c.187G>A) is associated with Inborn genetic diseases (ClinVar).

How common is NOVA2 p.Gly63Arg (c.187G>A) in the general population?

NOVA2 p.Gly63Arg (c.187G>A) is ultra-rare (popmax 0.0147%, amr) (gnomAD).

What do computational predictors say about NOVA2 p.Gly63Arg (c.187G>A)?

AlphaMissense predicts likely pathogenic (score 0.8168) — an in-silico prediction, not a clinical call.

NOVA2 p.Gly63Arg

c.187G>A · rs1027936364 · VCV2384839

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8168 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8168	likely pathogenic
REVEL	0.555	indeterminate
SaProt	LLR -9.96	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.6, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 33 kb · p 1.6e-21 · regional, not allelic
Overall
CADD	28.2	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

Grpmax group 0.0147% Admixed American · 8/54,362 alleles

Filtering AF 0.00731% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00525%

Overall 0.00266% 42/1,577,942 alleles · ultra-rare exomes 41/1,425,804 · genomes 1/152,138 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0147%	6,795
European (non-Finnish)	0.00284%	35,198
Remaining individualsnot grpmax-eligible	0.00164%	61,084

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.Gly63Arg
Coding: c.187G>A
MANE Select: NM_002516
dbSNP: rs1027936364
Type: single nucleotide variant
Location: chr19:45961052 (GRCh38)
Gene constraint: LOEUF 0.611 · pLI 0.85 (gnomAD)
Structure: AlphaFold pLDDT 65.60 · 2 PDB
Residue 63: the kh 1 domain

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.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
NOVA2 p.Ala362Thr 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-gly63arg (accessed [today's date]).

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