APTX p.Arg42Pro
c.125G>C · VCV3935480
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00439%, sas)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.502 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 4.8 | GERP 1.7, phastCons 1 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 16 kb · p 0.77 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00439%
South Asian · 4/91,074 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.000619%
10/1,614,226 alleles · very rare
exomes 10/1,461,874 · genomes 0/152,352 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00439% | 22,769 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,506 |
| European (non-Finnish) | 0.000424% | 236,009 |
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.Arg42Pro
- Coding
- c.125G>C
- MANE Select
- NM_001195248
- Type
- single nucleotide variant
- Location
- chr9:32989767 (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
Similar variants
- APTX p.Arg42Ter Conflicting classifications of pathogenicity ★ same residue
- APTX p.Arg29His Uncertain significance ★★ same condition
- APTX p.Arg3Gln Uncertain significance ★★ same condition
- APTX p.Asn120Ser Uncertain significance ★★ same condition
- APTX p.Glu103Lys Uncertain significance ★★ same condition
- APTX p.Glu131Lys Uncertain significance ★★ same condition
- APTX p.His320Leu Uncertain significance ★★ same condition
- APTX p.Ile124Leu 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-arg42pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown