Is NOVA2 p.Phe34Leu (c.102C>A) pathogenic?

NOVA2 p.Phe34Leu (c.102C>A) is classified Uncertain significance in NOVA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-07). AlphaMissense: likely pathogenic (0.9876); No allele count reported in gnomAD v4.1 (AN 1,598,410).

How common is NOVA2 p.Phe34Leu (c.102C>A) in the general population?

NOVA2 p.Phe34Leu (c.102C>A) is no allele count reported in gnomAD v4.1 (AN 1,598,410) (gnomAD).

What do computational predictors say about NOVA2 p.Phe34Leu (c.102C>A)?

AlphaMissense predicts likely pathogenic (score 0.9876) — an in-silico prediction, not a clinical call.

NOVA2 p.Phe34Leu

c.102C>A · rs2513865946 · VCV3252546

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9876 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,598,410)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9876	likely pathogenic
REVEL	0.236	benign-leaning
SaProt	LLR -7.75	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.6	GERP -1.6, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 33 kb · p 1.6e-21 · regional, not allelic
Overall
CADD	23.3	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 1,598,410). 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.Phe34Leu
Coding: c.102C>A
MANE Select: NM_002516
dbSNP: rs2513865946
Type: single nucleotide variant
Location: chr19:45961137 (GRCh38)
Gene constraint: LOEUF 0.611 · pLI 0.85 (gnomAD)
Structure: AlphaFold pLDDT 65.60 · 2 PDB
Residue 34: the kh 1 domain

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-phe34leu (accessed [today's date]).

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