Is GLDC p.Ser565= (c.1695G>A) pathogenic?

GLDC p.Ser565= (c.1695G>A) is classified Likely benign in GLDC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). Very rare (popmax 0.00549%, sas); Associated with glycine encephalopathy.

What condition is associated with GLDC p.Ser565= (c.1695G>A)?

GLDC p.Ser565= (c.1695G>A) is associated with glycine encephalopathy (ClinVar).

How common is GLDC p.Ser565= (c.1695G>A) in the general population?

GLDC p.Ser565= (c.1695G>A) is very rare (popmax 0.00549%, sas) (gnomAD).

How is Glycine encephalopathy inherited?

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

GLDC p.Ser565=

c.1695G>A · rs762780926 · VCV1092360

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

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 -0.94	GERP -3.1, phastCons 0.002
Overall
CADD	5.435	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,024 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00174% 28/1,611,766 alleles · very rare exomes 27/1,459,714 · genomes 1/152,052 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,205
East Asian	0.00223%	44,872
European (non-Finnish)	0.00178%	56,097
Remaining individualsnot grpmax-eligible	0.0016%	62,412

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.Ser565=
Coding: c.1695G>A
MANE Select: NM_000170
dbSNP: rs762780926
Type: single nucleotide variant
Location: chr9:6588413 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.50 · 3 PDB
Residue 565: 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.Ser565Ter 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
GLDC c.2315+2T>G 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-ser565 (accessed [today's date]).

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