Is GLDC p.Ser617= (c.1851C>T) pathogenic?

GLDC p.Ser617= (c.1851C>T) is classified Likely benign in GLDC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-24). Ultra-rare (popmax 0.0987%, mid); Associated with glycine encephalopathy.

What condition is associated with GLDC p.Ser617= (c.1851C>T)?

GLDC p.Ser617= (c.1851C>T) is associated with glycine encephalopathy (ClinVar).

How common is GLDC p.Ser617= (c.1851C>T) in the general population?

GLDC p.Ser617= (c.1851C>T) is ultra-rare (popmax 0.0987%, mid) (gnomAD).

How is Glycine encephalopathy inherited?

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

GLDC p.Ser617=

c.1851C>T · rs777724341 · VCV711425

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0987%, mid)

Conditions

glycine encephalopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.1	GERP -3.4
Overall
CADD	3.554	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0987% Middle Eastern · 6/6,082 alleles

Filtering AF 0.0429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00285% 46/1,611,474 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0987%	1,014
Remaining individualsnot grpmax-eligible	0.00641%	15,595
South Asian	0.0033%	30,345
European (non-Finnish)	0.00255%	39,256
East Asian	0.00223%	44,874
Finnishnot grpmax-eligible	0.00156%	64,030
African / African-American	0.00134%	74,900

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.Ser617=
Coding: c.1851C>T
MANE Select: NM_000170
dbSNP: rs777724341
Type: single nucleotide variant
Location: chr9:6565429 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.50 · 3 PDB

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.Ser617Thr Uncertain significance ★ ⚠ 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-ser617 (accessed [today's date]).

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