PMP2 p.Lys45=
c.135G>A · rs201891732 · VCV1592353
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0666%, amr)
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 0.81 | GERP -0.24, phastCons 1 |
| Overall | ||
| CADD | 8.376 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0666%
Admixed American · 40/60,026 alleles
Filtering AF
0.0502%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0446%
Overall
0.0282%
455/1,613,966 alleles · ultra-rare
exomes 421/1,461,634 · genomes 34/152,332 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0666% | 1,501 |
| European (non-Finnish) | 0.0329% | 3,041 |
| Remaining individualsnot grpmax-eligible | 0.0288% | 3,472 |
| African / African-American | 0.012% | 8,340 |
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
- PMP2
- Protein
- p.Lys45=
- Coding
- c.135G>A
- MANE Select
- NM_002677
- dbSNP
- rs201891732
- Type
- single nucleotide variant
- Location
- chr8:81444928 (GRCh38)
- Gene constraint
- LOEUF 1.511 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.49 · 30 PDB
- Residue 45
- a β-strand
Similar variants
- PMP2 p.Lys45Asn Uncertain significance ★ ⚠ same residue
- PMP2 p.Ile43Asn Pathogenic/Likely pathogenic ★★ same type
- PMP2 p.Ile52Thr Pathogenic/Likely pathogenic ★★ same type
- PMP2 p.Ala116= Uncertain significance ★★ same type
- PMP2 p.Arg53Gln Uncertain significance ★★ ⚠ same type
- PMP2 p.Asn60Thr Uncertain significance ★★ ⚠ same type
- PMP2 p.Asp19Asn Uncertain significance ★★ ⚠ same type
- PMP2 p.Asp48Asn Uncertain significance ★★ ⚠ 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/pmp2-p-lys45 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown