PMPCA p.Val4=
c.12G>C · VCV3609496
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00304%, 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 1.1 | GERP 1.2, phastCons 0.48 |
| Overall | ||
| CADD | 7.126 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00304%
European (non-Finnish) · 33/1,085,902 alleles
Filtering AF
0.00217%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00191%
Overall
0.00247%
35/1,414,770 alleles · very rare
exomes 33/1,262,526 · genomes 2/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00304% | 32,906 |
| Finnishnot grpmax-eligible | 0.002% | 50,094 |
| Remaining individualsnot grpmax-eligible | 0.00189% | 52,954 |
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.Val4=
- Coding
- c.12G>C
- MANE Select
- NM_015160
- Type
- single nucleotide variant
- Location
- chr9:136410680 (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.Lys4Gln Uncertain significance ★★ ⚠ same residue
- INPP5E p.Lys4Met Uncertain significance ★★ ⚠ same residue
- INPP5E p.Lys4= Likely benign ★★ same residue
- PMPCA p.Val4Glu 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
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-val4 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown