Is GLDC p.Pro110His (c.329C>A) pathogenic?

GLDC p.Pro110His (c.329C>A) is classified Conflicting classifications of pathogenicity in GLDC (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-04-27). AlphaMissense: likely benign (0.195); Ultra-rare (popmax 0.0774%, afr); Associated with glycine encephalopathy.

What condition is associated with GLDC p.Pro110His (c.329C>A)?

GLDC p.Pro110His (c.329C>A) is associated with glycine encephalopathy (ClinVar).

How common is GLDC p.Pro110His (c.329C>A) in the general population?

GLDC p.Pro110His (c.329C>A) is ultra-rare (popmax 0.0774%, afr) (gnomAD).

How is Glycine encephalopathy inherited?

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

What do computational predictors say about GLDC p.Pro110His (c.329C>A)?

AlphaMissense predicts likely benign (score 0.195) — an in-silico prediction, not a clinical call.

GLDC p.Pro110His

c.329C>A · rs371491621 · VCV575297

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.195 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0774%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

glycine encephalopathy

Computational evidence

Protein change
AlphaMissense	0.195	likely benign
REVEL	0.527	indeterminate
SaProt	LLR -11.44	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 112 kb · p 0.00071 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0774% African / African-American · 58/74,888 alleles

Filtering AF 0.0614% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0557%

Overall 0.0041% 66/1,608,270 alleles · ultra-rare exomes 36/1,455,992 · genomes 30/152,278 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0774%	1,291
Remaining individualsnot grpmax-eligible	0.0112%	8,903
Admixed American	0.00167%	60,014

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.Pro110His
Coding: c.329C>A
MANE Select: NM_000170
dbSNP: rs371491621
Type: single nucleotide variant
Location: chr9:6644619 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.50 · 3 PDB
Residue 110: 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.Pro110Ser 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-pro110his (accessed [today's date]).

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