Is NONO p.Pro260Arg (c.779C>G) pathogenic?

NONO p.Pro260Arg (c.779C>G) is classified Uncertain significance in NONO (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-07). AlphaMissense: likely pathogenic (0.9307); Absent from gnomAD v4.1.

How common is NONO p.Pro260Arg (c.779C>G) in the general population?

NONO p.Pro260Arg (c.779C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NONO p.Pro260Arg (c.779C>G)?

AlphaMissense predicts likely pathogenic (score 0.9307) — an in-silico prediction, not a clinical call.

NONO p.Pro260Arg

c.779C>G · VCV3602852

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9307 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9307	likely pathogenic
REVEL	0.72	pathogenic-leaning
SaProt	LLR -13.44	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2, phastCons 1
Regional constraint	o/e 0.16	constrained · MANE · 6,236 bp · p 7.9e-34 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Pro260Arg
Coding: c.779C>G
MANE Select: NM_007363
Type: single nucleotide variant
Location: chrX:71296883 (GRCh38)
Structure: AlphaFold pLDDT 77.76 · 9 PDB
Residue 260: the 'dbhs' region

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

Similar variants

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
NONO p.Gln380Arg 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-pro260arg (accessed [today's date]).

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