PMPCB p.Ala294=
c.882G>A · VCV3620517
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00683%, eas)
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 0.069 | GERP -3.7, phastCons 0.064 |
| Overall | ||
| CADD | 11.32 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00683%
East Asian · 3/43,896 alleles
Filtering AF
0.00181%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000902%
Overall
0.00131%
21/1,598,294 alleles · very rare
exomes 17/1,446,026 · genomes 4/152,268 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00683% | 14,632 |
| Admixed American | 0.00345% | 28,972 |
| South Asian | 0.00225% | 44,515 |
| European (non-Finnish) | 0.00119% | 83,704 |
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
- PMPCB
- Protein
- p.Ala294=
- Coding
- c.882G>A
- MANE Select
- NM_004279
- Type
- single nucleotide variant
- Location
- chr7:103308984 (GRCh38)
- Gene constraint
- LOEUF 1.085 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.48
Similar variants
- PMPCB p.Ala294Val Uncertain significance ★ ⚠ same residue
- PMPCB p.Arg175Cys Likely pathogenic ★★ same type
- PMPCB p.Arg209Gln Uncertain significance ★★ ⚠ same type
- PMPCB p.Arg325Cys Uncertain significance ★★ ⚠ same type
- PMPCB p.Arg451Ter Uncertain significance ★★ same type
- PMPCB p.Asn97Ser Uncertain significance ★★ ⚠ same type
- PMPCB p.Gln46Lys Uncertain significance ★★ ⚠ same type
- PMPCB p.Ile160Thr 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/pmpcb-p-ala294 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown