NGLY1 p.Pro293=
c.879A>G · VCV3620613
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00017%, nfe)
Conditions
1
congenital disorder of deglycosylation
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 -0.68 | phastCons 0.025 |
| Overall | ||
| CADD | 11.65 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00017%
European (non-Finnish) · 2/1,179,912 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000124%
2/1,613,978 alleles · very rare
exomes 2/1,461,682 · genomes 0/152,296 · 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
- NGLY1
- Protein
- p.Pro293=
- Coding
- c.879A>G
- MANE Select
- NM_018297
- Type
- single nucleotide variant
- Location
- chr3:25739579 (GRCh38)
- Gene constraint
- LOEUF 1.008 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.57 · 2 PDB
Similar variants
- NGLY1 p.Pro293Ala Uncertain significance ★ ⚠ same residue
- NGLY1 c.1150-1G>C Pathogenic/Likely pathogenic ★★ same condition
- NGLY1 c.658+1G>A Likely pathogenic ★★ same condition
- NGLY1 p.Arg291Ter Pathogenic/Likely pathogenic ★★ same condition
- NGLY1 p.Arg321Ter Pathogenic/Likely pathogenic ★★ same condition
- NGLY1 p.Arg390Ter Pathogenic ★★ same condition
- NGLY1 p.Arg401Ter Pathogenic/Likely pathogenic ★★ same condition
- NGLY1 p.Arg411Ter 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/ngly1-p-pro293 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown