Is NYX p.Pro170Arg (c.509C>G) pathogenic?

NYX p.Pro170Arg (c.509C>G) is classified Pathogenic in NYX (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-10-22). AlphaMissense: likely pathogenic (0.8876); Very rare (popmax 0.00012%, nfe); Associated with NYX-related disorder.

What condition is associated with NYX p.Pro170Arg (c.509C>G)?

NYX p.Pro170Arg (c.509C>G) is associated with NYX-related disorder, inherited retinal dystrophy (ClinVar).

How common is NYX p.Pro170Arg (c.509C>G) in the general population?

NYX p.Pro170Arg (c.509C>G) is very rare (popmax 0.00012%, nfe) (gnomAD).

What do computational predictors say about NYX p.Pro170Arg (c.509C>G)?

AlphaMissense predicts likely pathogenic (score 0.8876) — an in-silico prediction, not a clinical call.

NYX p.Pro170Arg

c.509C>G · rs62637025 · VCV99833

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8876 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00012%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

NYX-related disorder

Computational evidence

Protein change
AlphaMissense	0.8876	likely pathogenic ✓ concordant with ClinVar · top 9% in NYX
REVEL	0.8	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 0.59, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 27 kb · p 0.84 · regional, not allelic
Overall
CADD	25.1	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 P175R vs ClinVar P170R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00012% European (non-Finnish) · 1/836,717 alleles

Overall 9.26e-05% 1/1,079,928 alleles · very rare exomes 1/966,953 · genomes 0/112,975 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: NYX
Protein: p.Pro170Arg
Coding: c.509C>G
MANE Select: NM_001378477
dbSNP: rs62637025
Type: single nucleotide variant
Location: chrX:41473977 (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: inherited retinal dystrophy

Similar variants

NYX p.Pro170Leu Likely pathogenic ★ same residue
NYX p.Pro170Ser Likely pathogenic ★ same residue
NYX p.Pro170= Likely benign ★ same residue
NYX p.Asn211Ser Pathogenic/Likely pathogenic ★★ same condition
NYX p.Ser196Ter Pathogenic ★★ same condition
NYX p.Ser40Ter Pathogenic/Likely pathogenic ★★ same condition
NYX c.22+5G>T Pathogenic ★ same condition
NYX c.23-1G>T Pathogenic ★ 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-pro170arg (accessed [today's date]).

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