PMPCA p.Ala2=
c.6G>T · rs372181000 · VCV2889349
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0748%, mid)
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 3.7 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 12.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0748%
Middle Eastern · 4/5,346 alleles
Filtering AF
0.0255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0154%
Overall
0.00488%
69/1,413,944 alleles · ultra-rare
exomes 60/1,261,718 · genomes 9/152,226 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0748% | 1,336 |
| Admixed American | 0.0242% | 4,132 |
| Remaining individualsnot grpmax-eligible | 0.00945% | 10,584 |
| European (non-Finnish) | 0.00461% | 21,715 |
| African / African-American | 0.00298% | 33,568 |
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.Ala2=
- Coding
- c.6G>T
- MANE Select
- NM_015160
- dbSNP
- rs372181000
- Type
- single nucleotide variant
- Location
- chr9:136410674 (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.Pro2Ser Uncertain significance ★★ ⚠ same residue
- INPP5E p.Pro2= Likely benign ★ 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
- INPP5E p.Arg563His 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-ala2 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown