PMPCA p.Ala7=
c.21G>T · rs755775376 · VCV2981278
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00377%, nfe)
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 -0.11 | GERP 0.008 |
| Overall | ||
| CADD | 7.057 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00377%
European (non-Finnish) · 41/1,086,762 alleles
Filtering AF
0.00281%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00253%
Overall
0.00304%
43/1,416,430 alleles · very rare
exomes 38/1,264,200 · genomes 5/152,230 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00377% | 26,506 |
| South Asian | 0.00164% | 60,902 |
| African / African-American | 0.00149% | 67,138 |
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.Ala7=
- Coding
- c.21G>T
- MANE Select
- NM_015160
- dbSNP
- rs755775376
- Type
- single nucleotide variant
- Location
- chr9:136410689 (GRCh38)
- Gene constraint
- LOEUF 1.111 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 88.46
Similar variants
- PMPCA p.Ala7Glu Benign ★★ same residue
- INPP5E p.Asn7= Conflicting classifications of pathogenicity ★ same residue
- PMPCA p.Ala7Thr Uncertain significance ★ ⚠ same residue
- INPP5E p.Asn7fs Pathogenic ★ 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
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-ala7 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown