APTX p.Val259=
c.777A>C · rs1250575593 · VCV2198234
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00174%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.026 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -0.17 | GERP -2.3, phastCons 0.66 |
| Overall | ||
| CADD | 6.342 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00174%
Admixed American · 1/57,552 alleles
Filtering AF
8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.000378%
6/1,586,860 alleles · very rare
exomes 5/1,450,170 · genomes 1/136,690 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00174% | 57,552 |
| Remaining individualsnot grpmax-eligible | 0.00162% | 61,838 |
| European (non-Finnish) | 0.000343% | 291,758 |
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.Val259=
- Coding
- c.777A>C
- MANE Select
- NM_001195248
- dbSNP
- rs1250575593
- Type
- single nucleotide variant
- Location
- chr9:32974555 (GRCh38)
- Gene constraint
- LOEUF 0.973 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.52 · 11 PDB
- Residue 259
- the hit domain
Similar variants
- APTX p.Val259fs Pathogenic ★★ same residue
- APTX c.875-2A>G Pathogenic/Likely pathogenic ★★ same type
- APTX p.Ala198Val Likely pathogenic ★★ same type
- APTX p.Arg16Ter Pathogenic/Likely pathogenic ★★ same type
- APTX p.Arg247Ter Pathogenic/Likely pathogenic ★★ same type
- APTX p.Gln130Ter Pathogenic/Likely pathogenic ★★ same type
- APTX p.Gln187Ter Pathogenic ★★ same type
- APTX p.Trp279Arg Pathogenic/Likely pathogenic ★★ 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/aptx-p-val259 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown