PRX p.Ala8=
c.24C>T · rs748840915 · VCV2163570
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, mid)
Conditions
1
Charcot-Marie-Tooth disease type 4
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5 | GERP -4.7 |
| Overall | ||
| CADD | 1.277 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
Middle Eastern · 1/6,016 alleles
Filtering AF
0.00726%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00514%
Overall
0.000992%
16/1,613,466 alleles · ultra-rare
exomes 14/1,461,262 · genomes 2/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0166% | 6,016 |
| East Asian | 0.0156% | 6,413 |
| South Asian | 0.0022% | 45,542 |
| Admixed American | 0.00167% | 60,004 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,474 |
| European (non-Finnish) | 0.000339% | 295,009 |
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
- PRX
- Protein
- p.Ala8=
- Coding
- c.24C>T
- MANE Select
- NM_181882
- dbSNP
- rs748840915
- Type
- single nucleotide variant
- Location
- chr19:40407909 (GRCh38)
- Gene constraint
- LOEUF 1.321 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 35.74 · 1 PDB
Similar variants
- PRX c.184+2T>C Likely pathogenic ★★ same condition
- PRX p.Arg1070Ter Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Arg196Ter Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Arg364Ter Pathogenic ★★ same condition
- PRX p.Arg368Ter Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Arg392Ter Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Arg464Ter Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Arg897Ter Pathogenic/Likely pathogenic ★★ 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/prx-p-ala8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown