Is GLDC p.Val168= (c.504G>A) pathogenic?

GLDC p.Val168= (c.504G>A) is classified Likely benign in GLDC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-21). Very rare (popmax 0.00267%, afr); Associated with glycine encephalopathy.

What condition is associated with GLDC p.Val168= (c.504G>A)?

GLDC p.Val168= (c.504G>A) is associated with glycine encephalopathy (ClinVar).

How common is GLDC p.Val168= (c.504G>A) in the general population?

GLDC p.Val168= (c.504G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Glycine encephalopathy inherited?

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

GLDC p.Val168=

c.504G>A · rs151218113 · VCV1942037

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, 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 -1.4	GERP -0.43
Overall
CADD	5.688	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,940 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,613,544 alleles · very rare exomes 1/1,461,310 · genomes 2/152,234 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,470
European (non-Finnish)	8.48e-05%	1,179,554

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.Val168=
Coding: c.504G>A
MANE Select: NM_000170
dbSNP: rs151218113
Type: single nucleotide variant
Location: chr9:6610323 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.50 · 3 PDB
Residue 168: 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.Val168Ala Uncertain significance ★ ⚠ same residue
GLDC p.Val168Met 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

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-val168 (accessed [today's date]).

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