Is GCSH p.Pro30= (c.90C>G) pathogenic?

GCSH p.Pro30= (c.90C>G) is classified Benign in GCSH (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-22). Common (popmax 10.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with glycine encephalopathy.

What condition is associated with GCSH p.Pro30= (c.90C>G)?

GCSH p.Pro30= (c.90C>G) is associated with glycine encephalopathy (ClinVar).

How is Glycine encephalopathy inherited?

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

GCSH p.Pro30=

Q: How common is GCSH p.Pro30= (c.90C>G) in the general population?

GCSH p.Pro30= (c.90C>G) is common (popmax 10.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.90C>G · rs8177847 · VCV462910

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 10.3%, afr) — too common for a highly-penetrant pathogenic allele

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 0.72	GERP -0.21, phastCons 0.95
Overall
CADD	6.162	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.3% African / African-American · 6,679/65,012 alleles

Filtering AF 10.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.98%

Overall 0.733% 9,670/1,319,306 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.3%	10
Ashkenazi Jewishnot grpmax-eligible	3.23%	31
East Asian	1.71%	59
Middle Eastern	1.69%	59
Remaining individualsnot grpmax-eligible	1.18%	85
Admixed American	1.06%	94
South Asian	0.197%	508
European (non-Finnish)	0.0782%	1,279
Finnishnot grpmax-eligible	0.00801%	12,483

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: GCSH
Protein: p.Pro30=
Coding: c.90C>G
MANE Select: NM_004483
dbSNP: rs8177847
Type: single nucleotide variant
Location: chr16:81096189 (GRCh38)
Gene constraint: LOEUF 1.537 · pLI 0.33 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.49 · 3 PDB

Full GCSH 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

GCSH p.Pro30Leu Uncertain significance ★★ ⚠ same residue
GCSH p.Gln76Ter Pathogenic/Likely pathogenic ★★ same condition
GCSH p.Met1Val Pathogenic/Likely pathogenic ★★ same condition
GCSH p.Ala11Thr Uncertain significance ★★ ⚠ same condition
GCSH p.Ala2Pro Uncertain significance ★★ ⚠ same condition
GCSH p.Arg17Cys Uncertain significance ★★ ⚠ same condition
GCSH p.Arg7Trp Uncertain significance ★★ ⚠ same condition
GCSH p.Cys26Tyr Uncertain significance ★★ ⚠ 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/gcsh-p-pro30 (accessed [today's date]).

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