PMPCA p.Ser511=
c.1533G>A · VCV4140433
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0121%, sas)
Conditions
1
Inborn genetic diseases
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 |
|---|---|---|
| Pangolin | Δ0.26 | gain · loss 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP -7.4 | GERP -2.7 |
| Overall | ||
| CADD | 2.626 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0121%
South Asian · 11/91,084 alleles
Filtering AF
0.00676%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00522%
Overall
0.00149%
24/1,613,442 alleles · ultra-rare
exomes 23/1,461,194 · genomes 1/152,248 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0121% | 8,280 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,241 |
| East Asian | 0.00223% | 44,898 |
| Finnishnot grpmax-eligible | 0.00158% | 63,374 |
| European (non-Finnish) | 0.000763% | 131,115 |
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.Ser511=
- Coding
- c.1533G>A
- MANE Select
- NM_015160
- Type
- single nucleotide variant
- Location
- chr9:136423219 (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.Ile511= Likely benign same residue
- INPP5E p.Ala105Val Uncertain significance ★★ ⚠ same condition
- INPP5E p.Ala123Val Uncertain significance ★★ ⚠ same condition
- INPP5E p.Ala291Val Uncertain significance ★★ ⚠ same condition
- INPP5E p.Ala36Val Uncertain significance ★★ ⚠ same condition
- INPP5E p.Ala503Ser Uncertain significance ★★ ⚠ same condition
- INPP5E p.Arg251Pro Uncertain significance ★★ ⚠ same condition
- INPP5E p.Arg297Gln Uncertain significance ★★ ⚠ same condition
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-ser511 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown