Is GLDC p.Asp482fs (c.1444dup) pathogenic?

GLDC p.Asp482fs (c.1444dup) is classified Pathogenic in GLDC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-29). Very rare (popmax 0.000681%, nfe); Associated with glycine encephalopathy.

What condition is associated with GLDC p.Asp482fs (c.1444dup)?

GLDC p.Asp482fs (c.1444dup) is associated with glycine encephalopathy (ClinVar).

How common is GLDC p.Asp482fs (c.1444dup) in the general population?

GLDC p.Asp482fs (c.1444dup) is very rare (popmax 0.000681%, nfe) (gnomAD).

How is Glycine encephalopathy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

GLDC p.Asp482fs

c.1444dup · rs386833526 · VCV56045

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000681%, nfe)

Conditions

glycine encephalopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.5, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000681% European (non-Finnish) · 8/1,175,418 alleles

Filtering AF 0.000293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000212%

Overall 0.000549% 8/1,456,588 alleles · very rare

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: GLDC
Protein: p.Asp482fs
Coding: c.1444dup
MANE Select: NM_000170
dbSNP: rs386833526
Type: Duplication
Location: chr9:6592180 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.50 · 3 PDB
Residue 482: an α-helix

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

Disease context

glycine encephalopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycine encephalopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

GLDC p.Asp482= Likely benign ★★ same residue
GLDC p.Asp482Glu Uncertain significance ★ ⚠ same residue
GLDC p.Asp72fs Likely pathogenic ★★ same condition
GLDC p.Ile810fs Pathogenic/Likely pathogenic ★★ same condition
GLDC p.Tyr964Ter Pathogenic ★★ same condition
GLDC p.Ile147dup Uncertain significance ★★ same condition
GLDC c.2316-13_2316-12dup Benign/Likely benign ★★ same condition
GLDC c.2316-6dup Benign/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/gldc-p-asp482fs (accessed [today's date]).

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