Is GAMT p.Ile111fs (c.332_338del) pathogenic?

GAMT p.Ile111fs (c.332338del) is classified Pathogenic/Likely pathogenic in GAMT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-12). No gnomAD frequency available for this variant; Associated with guanidinoacetate methyltransferase deficiency.

How common is GAMT p.Ile111fs (c.332_338del) in the general population?

GAMT p.Ile111fs (c.332_338del) is no gnomAD frequency available for this variant (gnomAD).

GAMT p.Ile111fs

Q: What condition is associated with GAMT p.Ile111fs (c.332_338del)?

GAMT p.Ile111fs (c.332_338del) is associated with guanidinoacetate methyltransferase deficiency, cerebral creatine deficiency syndrome (ClinVar).

Q: How is Guanidinoacetate methyltransferase deficiency inherited?

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

c.332_338del · rs2512225602 · VCV2003951

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

guanidinoacetate methyltransferase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.7	GERP 0.46, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GAMT
Protein: p.Ile111fs
Coding: c.332_338del
MANE Select: NM_000156
dbSNP: rs2512225602
Type: Deletion
Location: chr19:1399577 (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 111: the rmt2 domain; a β-strand

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

Disease context

guanidinoacetate methyltransferase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cerebral creatine deficiency syndrome

For Guanidinoacetate methyltransferase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

GAMT p.Ile111Leu Uncertain significance ★★★ ⚠ same residue
GAMT p.Glu176fs Likely pathogenic ★★★ same condition
GAMT p.Gly164fs Pathogenic ★★★ same condition
GAMT p.Phe149fs Likely pathogenic ★★★ same condition
GAMT c.182-265_182-228del Benign ★★★ same condition
GAMT p.Ala103fs Pathogenic/Likely pathogenic ★★ same condition
GAMT p.Asp101fs Pathogenic/Likely pathogenic ★★ same condition
GAMT p.Gln97fs 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-ile111fs (accessed [today's date]).

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