PMPCA p.Arg525=
c.1575G>A · rs149519003 · VCV2673204
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00645%, 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 -0.01 | GERP -2.4, phastCons 0.39 |
| Overall | ||
| CADD | 4.765 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00645%
European (non-Finnish) · 76/1,178,788 alleles
Filtering AF
0.00528%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00482%
Overall
0.00497%
80/1,610,854 alleles · very rare
exomes 76/1,458,482 · genomes 4/152,372 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00645% | 15,510 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,578 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,200 |
| Admixed American | 0.00167% | 59,912 |
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.Arg525=
- Coding
- c.1575G>A
- MANE Select
- NM_015160
- dbSNP
- rs149519003
- Type
- single nucleotide variant
- Location
- chr9:136423261 (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.Arg525Gln Uncertain significance ★ ⚠ same residue
- PMPCA p.Arg525Trp 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
- 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-arg525 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown