PIGL p.Ser178=
c.534T>C · rs114145762 · VCV159713
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00933%, afr)
Conditions
1
CHIME syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.235 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -13 | GERP -3.5 |
| Overall | ||
| CADD | 0.014 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00933%
African / African-American · 7/75,062 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00308%
Overall
0.00062%
10/1,613,992 alleles · very rare
exomes 8/1,461,632 · genomes 2/152,360 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00933% | 10,723 |
| South Asian | 0.0022% | 45,534 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,480 |
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
- PIGL
- Protein
- p.Ser178=
- Coding
- c.534T>C
- MANE Select
- NM_004278
- dbSNP
- rs114145762
- Type
- single nucleotide variant
- Location
- chr17:16317782 (GRCh38)
- Gene constraint
- LOEUF 1.239 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.66
Similar variants
- PIGL c.427-1G>A Pathogenic ★★ same condition
- PIGL c.660+1G>T Likely pathogenic ★★ same condition
- PIGL p.Arg88Cys Likely pathogenic ★★ same condition
- PIGL p.Leu167Pro Pathogenic ★★ same condition
- PIGL p.Arg165= Uncertain significance ★★ same condition
- PIGL p.Arg242Pro Uncertain significance ★★ ⚠ same condition
- PIGL p.Arg242Trp Uncertain significance ★★ ⚠ same condition
- PIGL p.Arg88His 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/pigl-p-ser178 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown