NOVA2 p.Leu238=

Q: Is NOVA2 p.Leu238= (c.714G>T) pathogenic?

NOVA2 p.Leu238= (c.714G>T) is classified Benign in NOVA2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-09-05). Common (popmax 79.7%, eas) — 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.Leu238= (c.714G>T)?

NOVA2 p.Leu238= (c.714G>T) is associated with neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities (ClinVar).

Q: How common is NOVA2 p.Leu238= (c.714G>T) in the general population?

NOVA2 p.Leu238= (c.714G>T) is common (popmax 79.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.714G>T · rs1047061 · VCV1326995

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 79.7%, eas) — 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 0.51	GERP -5, phastCons 1
Overall
CADD	7.951	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 79.7% East Asian · 29,732/37,302 alleles

Filtering AF 78.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 78.6%

Overall 65.3% 962,699/1,473,314 alleles · common exomes 865,191/1,321,416 · genomes 97,508/151,898 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	79.7%	1
Finnishnot grpmax-eligible	74.1%	1
South Asian	69.8%	1
European (non-Finnish)	65%	2
Remaining individualsnot grpmax-eligible	64.8%	2
African / African-American	62%	2
Middle Eastern	60.2%	2
Ashkenazi Jewishnot grpmax-eligible	55.5%	2
Admixed American	55.4%	2
Amishnot grpmax-eligible	41.1%	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.Leu238=
Coding: c.714G>T
MANE Select: NM_002516
dbSNP: rs1047061
Type: single nucleotide variant
Location: chr19:45940628 (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.Leu238fs Pathogenic same residue
NOVA2 p.Ala287= 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

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-leu238 (accessed [today's date]).

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