Is APTX c.*454G>C pathogenic?

APTX c.454G>C is classified Benign in APTX (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Low-frequency (popmax 1.83%, afr); Associated with ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia.

What condition is associated with APTX c.*454G>C?

APTX c.*454G>C is associated with ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia (ClinVar).

How common is APTX c.*454G>C in the general population?

APTX c.*454G>C is low-frequency (popmax 1.83%, afr) (gnomAD).

How is Ataxia-oculomotor apraxia type 1 inherited?

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

APTX c.*454G>C

rs138490250 · VCV366586

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.83%, afr)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.9	GERP -2.4
Non-coding constraint	Z 0.27	1 kb window · o/e 0.98 · regional · uncalibrated
Overall
CADD	0.659	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.83% African / African-American · 917/50,126 alleles

Filtering AF 1.73% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.69%

Overall 0.226% 1,027/454,342 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.83%	55
Middle Eastern	0.208%	481
Admixed American	0.157%	636
Remaining individualsnot grpmax-eligible	0.136%	735
South Asian	0.00775%	12,896
European (non-Finnish)	0.00573%	17,458

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: APTX
Coding: c.*454G>C
MANE Select: NM_001195248
dbSNP: rs138490250
Type: single nucleotide variant
Location: chr9:32973044 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.52 · 11 PDB

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 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
APTX p.His166Tyr 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-c-star-454g-c (accessed [today's date]).

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