Is APTX p.Lys233Ter (c.697A>T) pathogenic?

APTX p.Lys233Ter (c.697A>T) is classified Pathogenic in APTX (ClinVar, No assertion criteria, 1 submitter). Absent from gnomAD v4.1; Associated with ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia.

What condition is associated with APTX p.Lys233Ter (c.697A>T)?

APTX p.Lys233Ter (c.697A>T) is associated with ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia (ClinVar).

How common is APTX p.Lys233Ter (c.697A>T) in the general population?

APTX p.Lys233Ter (c.697A>T) is absent from gnomAD v4.1 (gnomAD).

How is Ataxia-oculomotor apraxia type 1 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

APTX p.Lys233Ter

c.697A>T · rs1114167423 · VCV426093

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 8
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.59, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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: APTX
Protein: p.Lys233Ter
Coding: c.697A>T
MANE Select: NM_001195248
dbSNP: rs1114167423
Type: single nucleotide variant
Location: chr9:32984704 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.52 · 11 PDB
Residue 233: the hit domain; an α-helix

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

Disease context

ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Ataxia-oculomotor apraxia type 1 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

APTX p.Lys233Asn Uncertain significance ★ same residue
APTX c.875-2A>G Pathogenic/Likely pathogenic ★★ same condition
APTX p.Ala198Val Likely pathogenic ★★ same condition
APTX p.Arg16Ter Pathogenic/Likely pathogenic ★★ same condition
APTX p.Gln130Ter Pathogenic/Likely pathogenic ★★ same condition
APTX p.Trp279Ter Pathogenic ★★ same condition
APTX p.Arg247Gln Uncertain significance ★★ same condition
APTX p.Glu125Asp 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/aptx-p-lys233ter (accessed [today's date]).

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