Is NYX p.Arg89Pro (c.266G>C) pathogenic?

NYX p.Arg89Pro (c.266G>C) is classified Likely pathogenic in NYX (ClinVar, Single submitter, 2 submitters; last evaluated 2023-03-23). AlphaMissense: ambiguous (0.4887); No allele count reported in gnomAD v4.1 (AN 1,157,933); Associated with NYX-related disorder.

What condition is associated with NYX p.Arg89Pro (c.266G>C)?

NYX p.Arg89Pro (c.266G>C) is associated with NYX-related disorder, congenital stationary night blindness 1A (ClinVar).

How common is NYX p.Arg89Pro (c.266G>C) in the general population?

NYX p.Arg89Pro (c.266G>C) is no allele count reported in gnomAD v4.1 (AN 1,157,933) (gnomAD).

What do computational predictors say about NYX p.Arg89Pro (c.266G>C)?

AlphaMissense predicts ambiguous (score 0.4887) — an in-silico prediction, not a clinical call.

NYX p.Arg89Pro

c.266G>C · rs104894910 · VCV11424

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4887 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,157,933)

Conditions

NYX-related disorder

Computational evidence

Protein change
AlphaMissense	0.4887	ambiguous
REVEL	0.285	benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 0.54, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 27 kb · p 0.84 · regional, not allelic
Overall
CADD	25.7	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 R94P vs ClinVar R89P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,157,933). 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: NYX
Protein: p.Arg89Pro
Coding: c.266G>C
MANE Select: NM_001378477
dbSNP: rs104894910
Type: single nucleotide variant
Location: chrX:41473734 (GRCh38)
Structure: AlphaFold pLDDT 82.68

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

Disease context

NYX-related disorder

Also linked: congenital stationary night blindness 1A

Similar variants

NYX p.Asn211Ser Pathogenic/Likely pathogenic ★★ same condition
NYX p.Pro170Arg Pathogenic ★★ same condition
NYX p.Ser196Ter Pathogenic ★★ same condition
NYX p.Ser40Ter Pathogenic/Likely pathogenic ★★ same condition
NYX p.Ala123Val Uncertain significance ★★ ⚠ same condition
NYX p.Arg263Gly Uncertain significance ★★ ⚠ same condition
NYX p.Arg50Trp Uncertain significance ★★ same condition
NYX p.Asn233Lys Uncertain significance ★★ ⚠ 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/nyx-p-arg89pro (accessed [today's date]).

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