Is NGLY1 p.Phe379Ile (c.1135T>A) pathogenic?

NGLY1 p.Phe379Ile (c.1135T>A) is classified Uncertain significance in NGLY1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-07). AlphaMissense: ambiguous (0.4773); Absent from gnomAD v4.1; Associated with congenital disorder of deglycosylation.

What condition is associated with NGLY1 p.Phe379Ile (c.1135T>A)?

NGLY1 p.Phe379Ile (c.1135T>A) is associated with congenital disorder of deglycosylation (ClinVar).

How common is NGLY1 p.Phe379Ile (c.1135T>A) in the general population?

NGLY1 p.Phe379Ile (c.1135T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NGLY1 p.Phe379Ile (c.1135T>A)?

AlphaMissense predicts ambiguous (score 0.4773) — an in-silico prediction, not a clinical call.

NGLY1 p.Phe379Ile

c.1135T>A · rs2125475415 · VCV1431270

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4773 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

congenital disorder of deglycosylation

Computational evidence

Protein change
AlphaMissense	0.4773	ambiguous
REVEL	0.314	indeterminate
SaProt	LLR -9.14	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 64 kb · p 0.75 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NGLY1
Protein: p.Phe379Ile
Coding: c.1135T>A
MANE Select: NM_018297
dbSNP: rs2125475415
Type: single nucleotide variant
Location: chr3:25736018 (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

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-phe379ile (accessed [today's date]).

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