Is NAXE p.Cys158= (c.474T>C) pathogenic?

NAXE p.Cys158= (c.474T>C) is classified Likely benign in NAXE (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-17). Absent from gnomAD v4.1.

How common is NAXE p.Cys158= (c.474T>C) in the general population?

NAXE p.Cys158= (c.474T>C) is absent from gnomAD v4.1 (gnomAD).

NAXE p.Cys158=

c.474T>C · VCV4916434

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.45	GERP -4.3, phastCons 1
Overall
CADD	9.218	PHRED · no single calibrated threshold — expert panels disagree

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: NAXE
Protein: p.Cys158=
Coding: c.474T>C
MANE Select: NM_144772
Type: single nucleotide variant
Location: chr1:156592628 (GRCh38)
Gene constraint: LOEUF 1.079 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.71
Residue 158: a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy and developmental delay; uncertain significance); the yjef n-terminal domain

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

Similar variants

NAXE p.Cys158Ser Uncertain significance ★ ⚠ same residue
NAXE p.Cys158Tyr Uncertain significance ★ ⚠ same residue
NAXE c.664+2T>A Likely pathogenic ★★ same type
NAXE p.Ser43Ter Pathogenic ★★ same type
NAXE p.Arg197Gln Uncertain significance ★★ ⚠ same type
NAXE p.Arg254Cys Uncertain significance ★★ same type
NAXE p.Glu64Ala Uncertain significance ★★ ⚠ same type
NAXE p.Leu86Pro 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/naxe-p-cys158 (accessed [today's date]).

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