PIGN p.Leu392=
c.1176G>A · rs2513156952 · VCV2833114
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 9.52e-05%, nfe)
Conditions
1
multiple congenital anomalies-hypotonia-seizures syndrome 1
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 -1.8 | GERP -3.5 |
| Overall | ||
| CADD | 0.668 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
9.52e-05%
European (non-Finnish) · 1/1,050,100 alleles
Overall
6.94e-05%
1/1,440,300 alleles · very rare
exomes 1/1,288,120 · genomes 0/152,180 · joint denominator
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
- PIGN
- Protein
- p.Leu392=
- Coding
- c.1176G>A
- MANE Select
- NM_176787
- dbSNP
- rs2513156952
- Type
- single nucleotide variant
- Location
- chr18:62114636 (GRCh38)
- Gene constraint
- LOEUF 1.46 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 88.33
Similar variants
- PIGN c.1251+1G>A Pathogenic/Likely pathogenic ★★ same condition
- PIGN c.1252-2A>G Pathogenic/Likely pathogenic ★★ same condition
- PIGN c.1434+5G>A Pathogenic/Likely pathogenic ★★ same condition
- PIGN c.1574+1G>A Likely pathogenic ★★ same condition
- PIGN c.1674+1G>A Likely pathogenic ★★ same condition
- PIGN c.1674+1G>C Pathogenic ★★ same condition
- PIGN c.1675-1G>T Pathogenic/Likely pathogenic ★★ same condition
- PIGN c.222-1G>A Likely pathogenic ★★ 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/pign-p-leu392 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown