Is GLDC p.Val242= (c.726C>A) pathogenic?

GLDC p.Val242= (c.726C>A) is classified Likely benign in GLDC (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-20). Very rare (popmax 8.48e-05%, nfe); Associated with glycine encephalopathy.

What condition is associated with GLDC p.Val242= (c.726C>A)?

GLDC p.Val242= (c.726C>A) is associated with glycine encephalopathy (ClinVar).

How common is GLDC p.Val242= (c.726C>A) in the general population?

GLDC p.Val242= (c.726C>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Glycine encephalopathy inherited?

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

GLDC p.Val242=

c.726C>A · rs377750481 · VCV1081680

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 0.79	GERP -2.8, phastCons 1
Overall
CADD	3.337	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,778 alleles

Overall 0.000868% 14/1,613,752 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0187%	5,336
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)grpmax	8.48e-05%	1,179,778

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val242=
Coding: c.726C>A
MANE Select: NM_000170
dbSNP: rs377750481
Type: single nucleotide variant
Location: chr9:6605266 (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.Val242Ile 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-val242 (accessed [today's date]).

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