Is GAMT p.Pro18= (c.54C>G) pathogenic?

GAMT p.Pro18= (c.54C>G) is classified Likely benign in GAMT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-10). Very rare (popmax 9.13e-05%, nfe); Associated with cerebral creatine deficiency syndrome.

What condition is associated with GAMT p.Pro18= (c.54C>G)?

GAMT p.Pro18= (c.54C>G) is associated with cerebral creatine deficiency syndrome (ClinVar).

How common is GAMT p.Pro18= (c.54C>G) in the general population?

GAMT p.Pro18= (c.54C>G) is very rare (popmax 9.13e-05%, nfe) (gnomAD).

GAMT p.Pro18=

c.54C>G · rs960874258 · VCV2021971

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 9.13e-05%, nfe)

Conditions

cerebral creatine deficiency syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.38	GERP -3, phastCons 0.003
Overall
CADD	12.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.13e-05% European (non-Finnish) · 1/1,095,840 alleles

Overall 6.96e-05% 1/1,437,222 alleles · very rare exomes 1/1,285,020 · genomes 0/152,202 · joint denominator

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: GAMT
Protein: p.Pro18=
Coding: c.54C>G
MANE Select: NM_000156
dbSNP: rs960874258
Type: single nucleotide variant
Location: chr19:1401423 (GRCh38)
Gene constraint: LOEUF 1.536 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.73 · 1 PDB
Residue 18: the rmt2 domain; an α-helix

Full GAMT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cerebral creatine deficiency syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GAMT c.328-1G>A Pathogenic ★★★ same condition
GAMT c.328-2A>G Pathogenic ★★★ same condition
GAMT c.391+15G>T Likely pathogenic ★★★ same condition
GAMT c.391+1G>C Pathogenic ★★★ same condition
GAMT c.391+5G>C Likely pathogenic ★★★ same condition
GAMT p.Ala156Asp Likely pathogenic ★★★ same condition
GAMT p.Ala74Pro Likely pathogenic ★★★ same condition
GAMT p.Ala75Val 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/gamt-p-pro18 (accessed [today's date]).

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