PYGL p.Leu623=
c.1869G>C · rs745556673 · VCV3056555
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
1
PYGL-related disorder
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 -0.54 | GERP -0.66, phastCons 0.019 |
| Overall | ||
| CADD | 6.93 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,852 alleles
Overall
6.2e-05%
1/1,613,724 alleles · very rare
exomes 0/1,461,876 · genomes 1/151,848 · 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
- PYGL
- Protein
- p.Leu623=
- Coding
- c.1869G>C
- MANE Select
- NM_002863
- dbSNP
- rs745556673
- Type
- single nucleotide variant
- Location
- chr14:50911830 (GRCh38)
- Gene constraint
- LOEUF 1.048 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.87 · 19 PDB
- Residue 623
- an α-helix
Disease context
PYGL-related disorder
Similar variants
- PYGL p.Arg576Ter Pathogenic ★★ same condition
- PYGL p.Val456Met Pathogenic/Likely pathogenic ★★ same condition
- PYGL c.424+1G>T Likely pathogenic ★ same condition
- PYGL p.Gln823Ter Conflicting classifications of pathogenicity ★ same condition
- PYGL c.1093-3C>T Likely benign same condition
- PYGL c.1827+8G>A Likely benign same condition
- PYGL p.Ala729= Likely benign same condition
- PYGL p.Gly138= Likely benign 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/pygl-p-leu623 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown