Is NGLY1 p.Ser267= (c.801T>C) pathogenic?

NGLY1 p.Ser267= (c.801T>C) is classified Likely benign in NGLY1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-02). Very rare (popmax 0.00102%, nfe); Associated with congenital disorder of deglycosylation.

What condition is associated with NGLY1 p.Ser267= (c.801T>C)?

NGLY1 p.Ser267= (c.801T>C) is associated with congenital disorder of deglycosylation, congenital disorder of deglycosylation 1 (ClinVar).

How common is NGLY1 p.Ser267= (c.801T>C) in the general population?

NGLY1 p.Ser267= (c.801T>C) is very rare (popmax 0.00102%, nfe) (gnomAD).

NGLY1 p.Ser267=

c.801T>C · rs199578758 · VCV1149251

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Conditions

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 0.25	GERP -3.5
Overall
CADD	4.862	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,180,012 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000744% 12/1,613,974 alleles · very rare exomes 11/1,461,864 · genomes 1/152,110 · 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.Ser267=
Coding: c.801T>C
MANE Select: NM_018297
dbSNP: rs199578758
Type: single nucleotide variant
Location: chr3:25739657 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.57 · 2 PDB

Full NGLY1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital disorder of deglycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital disorder of deglycosylation 1

Similar variants

NGLY1 p.Ser267Ile 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.Arg328Cys Likely pathogenic ★★ same condition
NGLY1 p.Arg390Ter Pathogenic ★★ same condition
NGLY1 p.Arg401Ter Pathogenic/Likely 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-ser267 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown