PMPCA p.Pro355=
c.1065C>T · rs553050557 · VCV2895257
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.163%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3 |
| Overall | ||
| CADD | 1.015 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.163%
East Asian · 73/44,884 alleles
Filtering AF
0.133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.122%
Overall
0.0083%
134/1,613,732 alleles · rare
exomes 112/1,461,378 · genomes 22/152,354 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.163% | 615 |
| African / African-American | 0.0187% | 5,361 |
| Middle Eastern | 0.0165% | 6,060 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,813 |
| Admixed American | 0.00666% | 15,008 |
| European (non-Finnish) | 0.00288% | 34,694 |
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
- PMPCA
- Protein
- p.Pro355=
- Coding
- c.1065C>T
- MANE Select
- NM_015160
- dbSNP
- rs553050557
- Type
- single nucleotide variant
- Location
- chr9:136418629 (GRCh38)
- Gene constraint
- LOEUF 1.111 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 88.46
Similar variants
- INPP5E p.Thr355= Likely benign ★★ same residue
- INPP5E p.Thr355Met Conflicting classifications of pathogenicity ★ ⚠ same residue
- INPP5E p.Thr355_Leu356insArgLeuGlnAspThr Uncertain significance ★ same residue
- INPP5E c.937-2A>G Pathogenic/Likely pathogenic ★★ same type
- INPP5E p.Arg378Cys Pathogenic/Likely pathogenic ★★ same type
- INPP5E p.Arg435Gln Pathogenic/Likely pathogenic ★★ same type
- INPP5E p.Arg435Trp Pathogenic/Likely pathogenic ★★ same type
- INPP5E p.Arg557His Pathogenic/Likely pathogenic ★★ 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/pmpca-p-pro355 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown