Is GLDC p.Cys644= (c.1932C>T) pathogenic?

GLDC p.Cys644= (c.1932C>T) is classified Likely benign in GLDC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-12). Ultra-rare (popmax 0.096%, afr); Associated with glycine encephalopathy.

What condition is associated with GLDC p.Cys644= (c.1932C>T)?

GLDC p.Cys644= (c.1932C>T) is associated with glycine encephalopathy (ClinVar).

How common is GLDC p.Cys644= (c.1932C>T) in the general population?

GLDC p.Cys644= (c.1932C>T) is ultra-rare (popmax 0.096%, afr) (gnomAD).

How is Glycine encephalopathy inherited?

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

GLDC p.Cys644=

c.1932C>T · rs111348076 · VCV462863

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.096%, afr)

Conditions

glycine encephalopathy

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 2.5	GERP -0.072, phastCons 1
Overall
CADD	5.511	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.096% African / African-American · 72/75,018 alleles

Filtering AF 0.0781% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0716%

Overall 0.00595% 96/1,614,126 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.096%	1,042
Middle Eastern	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.016%	6,250
Admixed American	0.00666%	15,006
South Asian	0.0011%	91,086
European (non-Finnish)	0.000508%	196,667

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.Cys644=
Coding: c.1932C>T
MANE Select: NM_000170
dbSNP: rs111348076
Type: single nucleotide variant
Location: chr9:6558679 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.50 · 3 PDB
Residue 644: a β-strand

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.Cys644Tyr Pathogenic/Likely pathogenic ★★ same residue
GLDC p.Cys644Phe Likely pathogenic same residue
GLDC c.1401+1G>A Pathogenic/Likely pathogenic ★★ same condition
GLDC c.1580+2T>G Pathogenic ★★ same condition
GLDC c.1851-1G>A Pathogenic ★★ same condition
GLDC c.2053-2A>G Likely pathogenic ★★ same condition
GLDC c.2203-2A>G Pathogenic/Likely pathogenic ★★ same condition
GLDC c.2315+2T>A 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/gldc-p-cys644 (accessed [today's date]).

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