Is NYX p.Arg330Cys (c.988C>T) pathogenic?

NYX p.Arg330Cys (c.988C>T) is classified Uncertain significance in NYX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-07). AlphaMissense: likely benign (0.1822); Very rare (popmax 0.00651%, amr).

How common is NYX p.Arg330Cys (c.988C>T) in the general population?

NYX p.Arg330Cys (c.988C>T) is very rare (popmax 0.00651%, amr) (gnomAD).

What do computational predictors say about NYX p.Arg330Cys (c.988C>T)?

AlphaMissense predicts likely benign (score 0.1822) — an in-silico prediction, not a clinical call.

NYX p.Arg330Cys

c.988C>T · VCV3704500

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1822 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00651%, amr)

Computational evidence

Protein change
AlphaMissense	0.1822	likely benign
REVEL	0.621	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 27 kb · p 0.84 · regional, not allelic
Overall
CADD	27.0	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 R335C vs ClinVar R330C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00651% Admixed American · 3/46,069 alleles

Filtering AF 0.00173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000879%

Overall 0.00132% 16/1,209,052 alleles · very rare exomes 16/1,095,062 · genomes 0/113,990 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00651%	15,356
European (non-Finnish)	0.00145%	68,880

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.Arg330Cys
Coding: c.988C>T
MANE Select: NM_001378477
Type: single nucleotide variant
Location: chrX:41474456 (GRCh38)
Structure: AlphaFold pLDDT 82.68

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

Similar variants

NYX p.Arg330Leu Uncertain significance ★ 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
NYX p.Ala123Val 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-arg330cys (accessed [today's date]).

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