NGLY1 p.Phe80=
c.240T>C · rs1480280238 · VCV2093827
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00269%, afr)
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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 8.1 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 11.66 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00269%
African / African-American · 2/74,454 alleles
Filtering AF
0.000446%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000167%
Overall
0.000312%
5/1,602,948 alleles · very rare
exomes 3/1,450,710 · genomes 2/152,238 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00269% | 37,227 |
| South Asian | 0.00224% | 44,735 |
| Admixed American | 0.0017% | 58,868 |
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.Phe80=
- Coding
- c.240T>C
- MANE Select
- NM_018297
- dbSNP
- rs1480280238
- Type
- single nucleotide variant
- Location
- chr3:25778580 (GRCh38)
- Gene constraint
- LOEUF 1.008 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.57 · 2 PDB
- Residue 80
- the pub domain
Similar variants
- 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
- NGLY1 p.Arg469Ter 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-phe80 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown