APTX p.Leu317Phe
c.949C>T · rs1047315004 · VCV3128100
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0493%, mid)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.722 | pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 9.7 | GERP 1.4, phastCons 1 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 16 kb · p 0.77 · regional, not allelic |
| Overall | ||
| CADD | 28.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0493%
Middle Eastern · 3/6,084 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00715%
Overall
0.000186%
3/1,613,890 alleles · ultra-rare
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.Leu317Phe
- Coding
- c.949C>T
- MANE Select
- NM_001195248
- dbSNP
- rs1047315004
- Type
- single nucleotide variant
- Location
- chr9:32973578 (GRCh38)
- Gene constraint
- LOEUF 0.973 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.52 · 11 PDB
- Residue 317
- an α-helix
Similar variants
- 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
- APTX p.Ile17Phe 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-leu317phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown