Is NYX p.Arg263Pro (c.788G>C) pathogenic?

NYX p.Arg263Pro (c.788G>C) is classified Uncertain significance in NYX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-16). AlphaMissense: likely benign (0.2881); Absent from gnomAD v4.1.

How common is NYX p.Arg263Pro (c.788G>C) in the general population?

NYX p.Arg263Pro (c.788G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NYX p.Arg263Pro (c.788G>C)?

AlphaMissense predicts likely benign (score 0.2881) — an in-silico prediction, not a clinical call.

NYX p.Arg263Pro

c.788G>C · VCV4738994

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2881 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.2881	likely benign
REVEL	0.396	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -3.8
Regional constraint	o/e 0.99	unconstrained · MANE · 27 kb · p 0.84 · regional, not allelic
Overall
CADD	0.688	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R268P vs ClinVar R263P) — verify the residue.

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: NYX
Protein: p.Arg263Pro
Coding: c.788G>C
MANE Select: NM_001378477
Type: single nucleotide variant
Location: chrX:41474256 (GRCh38)
Structure: AlphaFold pLDDT 82.68

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

Similar variants

NYX p.Arg263Gly Uncertain significance ★★ ⚠ same residue
NYX p.Arg263= Likely benign ★ same residue
NYX p.Asn211Ser Pathogenic/Likely pathogenic ★★ same type
NYX p.Pro170Arg Pathogenic ★★ same type
NYX p.Ser196Ter Pathogenic ★★ same type
NYX p.Ser40Ter Pathogenic/Likely pathogenic ★★ same type
NYX p.Ala113Thr Uncertain significance ★★ same type
NYX p.Ala113Val 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/nyx-p-arg263pro (accessed [today's date]).

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