NOVA2 p.Ala287=

Q: Is NOVA2 p.Ala287= (c.861A>C) pathogenic?

NOVA2 p.Ala287= (c.861A>C) is classified Benign in NOVA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-09-05). Common (popmax 80.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities.

Q: What condition is associated with NOVA2 p.Ala287= (c.861A>C)?

NOVA2 p.Ala287= (c.861A>C) is associated with neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities (ClinVar).

Q: How common is NOVA2 p.Ala287= (c.861A>C) in the general population?

NOVA2 p.Ala287= (c.861A>C) is common (popmax 80.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.861A>C · rs28742045 · VCV1326984

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 80.8%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 1.5, phastCons 1
Overall
CADD	11.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 80.8% African / African-American · 55,960/69,282 alleles

Filtering AF 80.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 80%

Overall 70.1% 1,072,538/1,530,170 alleles · common exomes 963,682/1,379,552 · genomes 108,856/150,618 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	80.8%	1
East Asian	79.6%	1
Finnishnot grpmax-eligible	78.6%	1
South Asian	71.2%	1
Remaining individualsnot grpmax-eligible	69.7%	1
European (non-Finnish)	69.6%	1
Middle Eastern	64.5%	2
Ashkenazi Jewishnot grpmax-eligible	58.5%	2
Admixed American	56%	2
Amishnot grpmax-eligible	43.6%	2

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.Ala287=
Coding: c.861A>C
MANE Select: NM_002516
dbSNP: rs28742045
Type: single nucleotide variant
Location: chr19:45940481 (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

neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NOVA2 p.Leu238= Benign ★★ same condition
NOVA2 p.Gly31Ala Uncertain significance ★ ⚠ same condition
NOVA2 p.Thr124Met Conflicting classifications of pathogenicity ★ ⚠ same condition
NOVA2 p.Val156Met Conflicting classifications of pathogenicity ★ ⚠ same condition
NOVA2 p.Pro230Leu Uncertain significance ⚠ same condition
NOVA2 p.Gly219fs Likely pathogenic ★ same condition
NOVA2 p.Leu175fs Pathogenic ★ same condition
NOVA2 p.Tyr330fs Pathogenic ★ 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-ala287 (accessed [today's date]).

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