Is NONO p.Pro430Arg (c.1289C>G) pathogenic?

NONO p.Pro430Arg (c.1289C>G) is classified Uncertain significance in NONO (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-29). AlphaMissense: likely pathogenic (0.7034); Absent from gnomAD v4.1.

How common is NONO p.Pro430Arg (c.1289C>G) in the general population?

NONO p.Pro430Arg (c.1289C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NONO p.Pro430Arg (c.1289C>G)?

AlphaMissense predicts likely pathogenic (score 0.7034) — an in-silico prediction, not a clinical call.

NONO p.Pro430Arg

c.1289C>G · VCV3393576

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7034 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7034	likely pathogenic
REVEL	0.271	benign-leaning
SaProt	LLR -6.20	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 2, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 3,077 bp · p 2.4e-12 · regional, not allelic
Overall
CADD	23.0	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: NONO
Protein: p.Pro430Arg
Coding: c.1289C>G
MANE Select: NM_007363
Type: single nucleotide variant
Location: chrX:71299949 (GRCh38)
Structure: AlphaFold pLDDT 77.76 · 9 PDB

Full NONO gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NONO p.Pro430fs Pathogenic ★ same residue
NONO c.651-1G>C Likely pathogenic ★★ same type
NONO p.Ala377= Pathogenic ★★ same type
NONO p.Arg184Ter Pathogenic ★★ same type
NONO p.Ala453Pro Uncertain significance ★★ ⚠ same type
NONO p.Arg202Trp Uncertain significance ★★ ⚠ same type
NONO p.Arg456Ser Uncertain significance ★★ ⚠ same type
NONO p.Asn161Asp Uncertain significance ★★ ⚠ 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/nono-p-pro430arg (accessed [today's date]).

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