PYGL p.Pro230=
c.690C>T · rs141500790 · VCV730827
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.028%, afr)
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 -20 | GERP -3.9 |
| Overall | ||
| CADD | 0.005 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.028%
African / African-American · 21/74,918 alleles
Filtering AF
0.0188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0157%
Overall
0.00242%
39/1,613,964 alleles · ultra-rare
exomes 22/1,461,784 · genomes 17/152,180 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.028% | 3,568 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,828 |
| Admixed American | 0.00333% | 30,001 |
| South Asian | 0.0022% | 45,541 |
| European (non-Finnish) | 0.000932% | 107,268 |
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
- PYGL
- Protein
- p.Pro230=
- Coding
- c.690C>T
- MANE Select
- NM_002863
- dbSNP
- rs141500790
- Type
- single nucleotide variant
- Location
- chr14:50921038 (GRCh38)
- Gene constraint
- LOEUF 1.048 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.87 · 19 PDB
- Residue 230
- a β-strand
Similar variants
- PYGL c.1404-1G>A Pathogenic/Likely pathogenic ★★ same type
- PYGL c.1620+1G>A Pathogenic/Likely pathogenic ★★ same type
- PYGL c.1620+1G>C Pathogenic ★★ same type
- PYGL c.1768+1G>A Pathogenic ★★ same type
- PYGL c.772+1G>A Pathogenic/Likely pathogenic ★★ same type
- PYGL p.Arg576Ter Pathogenic ★★ same type
- PYGL p.Arg94Ter Pathogenic ★★ same type
- PYGL p.Gln577Ter 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/pygl-p-pro230 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown