Is NOVA2 p.Glu30Lys (c.88G>A) pathogenic?

NOVA2 p.Glu30Lys (c.88G>A) is classified Uncertain significance in NOVA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-18). AlphaMissense: ambiguous (0.5556); Absent from gnomAD v4.1.

How common is NOVA2 p.Glu30Lys (c.88G>A) in the general population?

NOVA2 p.Glu30Lys (c.88G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NOVA2 p.Glu30Lys (c.88G>A)?

AlphaMissense predicts ambiguous (score 0.5556) — an in-silico prediction, not a clinical call.

NOVA2 p.Glu30Lys

c.88G>A · rs1167129503 · VCV1697055

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5556 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5556	ambiguous
REVEL	0.166	moderately benign-leaning
SaProt	LLR -6.51	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 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	24.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NOVA2
Protein: p.Glu30Lys
Coding: c.88G>A
MANE Select: NM_002516
dbSNP: rs1167129503
Type: single nucleotide variant
Location: chr19:45961151 (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-glu30lys (accessed [today's date]).

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