Is NYX p.Ser94Phe (c.281C>T) pathogenic?

NYX p.Ser94Phe (c.281C>T) is classified Conflicting classifications of pathogenicity in NYX (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-29). AlphaMissense: likely pathogenic (0.8712); Ultra-rare (popmax 0.0237%, mid); Associated with Inborn genetic diseases.

What condition is associated with NYX p.Ser94Phe (c.281C>T)?

NYX p.Ser94Phe (c.281C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NYX p.Ser94Phe (c.281C>T) in the general population?

NYX p.Ser94Phe (c.281C>T) is ultra-rare (popmax 0.0237%, mid) (gnomAD).

What do computational predictors say about NYX p.Ser94Phe (c.281C>T)?

AlphaMissense predicts likely pathogenic (score 0.8712) — an in-silico prediction, not a clinical call.

NYX p.Ser94Phe

c.281C>T · rs777112148 · VCV955555

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8712 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0237%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8712	likely pathogenic · top 10% in NYX
REVEL	0.476	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP -0.33, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 27 kb · p 0.84 · regional, not allelic
Overall
CADD	25.3	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 S99F vs ClinVar S94F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0237% Middle Eastern · 1/4,215 alleles

Filtering AF 0.000168% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000122%

Overall 0.000606% 7/1,154,721 alleles · ultra-rare exomes 6/1,043,238 · genomes 1/111,483 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0237%	4,215
Remaining individualsnot grpmax-eligible	0.00221%	45,205
European (non-Finnish)	0.000573%	174,650

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.Ser94Phe
Coding: c.281C>T
MANE Select: NM_001378477
dbSNP: rs777112148
Type: single nucleotide variant
Location: chrX:41473749 (GRCh38)
Structure: AlphaFold pLDDT 82.68

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NYX p.Ala113Val Uncertain significance ★★ same condition
NYX p.Ala151Thr Uncertain significance ★★ ⚠ same condition
NYX p.Ala265Thr Uncertain significance ★★ ⚠ same condition
NYX p.Ala267Val Uncertain significance ★★ ⚠ same condition
NYX p.Ala28Thr Uncertain significance ★★ ⚠ same condition
NYX p.Ala31Asp Uncertain significance ★★ ⚠ same condition
NYX p.Ala53Val Uncertain significance ★★ ⚠ same condition
NYX p.Arg119His 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-ser94phe (accessed [today's date]).

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