PMPCA p.Asp514=
c.1542C>T · rs761386835 · VCV711534
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0183%, amr)
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 -8 | GERP -2.7 |
| Overall | ||
| CADD | 1.888 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0183%
Admixed American · 11/60,010 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00785%
Overall
0.00329%
53/1,613,324 alleles · ultra-rare
exomes 48/1,461,080 · genomes 5/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0183% | 5,455 |
| Finnishnot grpmax-eligible | 0.00474% | 21,089 |
| East Asian | 0.00445% | 22,449 |
| African / African-American | 0.004% | 24,985 |
| European (non-Finnish) | 0.00271% | 36,876 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,478 |
| South Asian | 0.0011% | 91,092 |
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.Asp514=
- Coding
- c.1542C>T
- MANE Select
- NM_015160
- dbSNP
- rs761386835
- Type
- single nucleotide variant
- Location
- chr9:136423228 (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.Asp514Gly 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
- INPP5E p.Arg585Cys 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-asp514 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown