PRX p.Pro606=
c.1818G>A · rs768022787 · VCV893793
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0044%, sas)
Conditions
3
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 -20 | GERP -4.1 |
| Overall | ||
| CADD | 0.283 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0044%
South Asian · 4/90,972 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000892%
Overall
0.000496%
8/1,612,282 alleles · very rare
exomes 7/1,461,876 · genomes 1/150,406 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0044% | 22,743 |
| African / African-American | 0.00135% | 74,318 |
| European (non-Finnish) | 0.000254% | 393,181 |
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.Pro606=
- Coding
- c.1818G>A
- MANE Select
- NM_181882
- dbSNP
- rs768022787
- Type
- single nucleotide variant
- Location
- chr19:40396534 (GRCh38)
- Gene constraint
- LOEUF 1.321 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 35.74 · 1 PDB
- Residue 606
- the '55 x 5 aa approximate tandem repeats of [lvmag]-[psreqc]-[edkl]-[livmap]-[aqkhrpe]; that may have a tripeptide spacer of [lv]-p-[ker]' region
Similar variants
- PRX p.Pro606Leu Uncertain significance ★ ⚠ same residue
- 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
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-pro606 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown