APTX p.Arg42Ter
c.124C>T · rs201912053 · VCV420789
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 2 of 8 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.7 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 40.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.0574% | 1,742 |
| Middle Easterngrpmax | 0.0164% | 6,084 |
| Admixed American | 0.005% | 20,001 |
| East Asian | 0.00445% | 22,450 |
| African / African-American | 0.00267% | 37,462 |
| European (non-Finnish) | 0.00161% | 62,108 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| South Asian | 0.0011% | 91,082 |
Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- Protein
- p.Arg42Ter
- Coding
- c.124C>T
- MANE Select
- NM_001195248
- dbSNP
- rs201912053
- Type
- single nucleotide variant
- Location
- chr9:32989768 (GRCh38)
- Gene constraint
- LOEUF 0.973 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.52 · 11 PDB
- Residue 42
- the fha-like domain; the 'interactions with adprt/parp1 and ncl' region
Disease context
ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Ataxia-oculomotor apraxia type 1 (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Childhood
Similar variants
- APTX p.Arg42Pro 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-arg42ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown