APTX p.Arg245His
c.734G>A · rs747334007 · VCV214121
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00549%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.348 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.25 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -0.008 | GERP 0.75, phastCons 0.08 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 16 kb · p 0.77 · regional, not allelic |
| Overall | ||
| CADD | 20.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00549%
South Asian · 5/91,088 alleles
Filtering AF
0.0021%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00136%
Overall
0.00178%
26/1,461,890 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00549% | 18,218 |
| African / African-American | 0.004% | 25,013 |
| East Asian | 0.00223% | 44,882 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,510 |
| European (non-Finnish) | 0.00136% | 73,752 |
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.Arg245His
- Coding
- c.734G>A
- MANE Select
- NM_001195248
- dbSNP
- rs747334007
- Type
- single nucleotide variant
- Location
- chr9:32984667 (GRCh38)
- Gene constraint
- LOEUF 0.973 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.52 · 11 PDB
- Residue 245
- the hit domain; an α-helix
Similar variants
- APTX p.Arg245Cys Uncertain significance ★ 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-arg245his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown