Is GAMT p.Asp93= (c.279C>T) pathogenic?

GAMT p.Asp93= (c.279C>T) is classified Benign in GAMT (ClinVar, Expert panel, 11 submitters; last evaluated 2022-06-06). Rare (popmax 0.257%, eas); Associated with guanidinoacetate methyltransferase deficiency.

What condition is associated with GAMT p.Asp93= (c.279C>T)?

GAMT p.Asp93= (c.279C>T) is associated with guanidinoacetate methyltransferase deficiency, cerebral creatine deficiency syndrome (ClinVar).

How common is GAMT p.Asp93= (c.279C>T) in the general population?

GAMT p.Asp93= (c.279C>T) is rare (popmax 0.257%, eas) (gnomAD).

GAMT p.Asp93=

Q: How is Guanidinoacetate methyltransferase deficiency inherited?

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

c.279C>T · rs144630886 · VCV137434

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

rare (popmax 0.257%, eas)

Conditions

guanidinoacetate methyltransferase deficiency

ClinGen expert panel — Cerebral Creatine Deficiency Syndromes VCEP

Benign for guanidinoacetate methyltransferase deficiency. Applied ACMG criteria (verbatim):

BP7 BP4 BA1

Curation rationale (ClinGen, verbatim)

The NM_000156.6:c.279C>T (p.Asp93=) is a synonymous variant in GAMT that is predicted to not impact splicing by SpliceAI and VarSeak, and the nucleotide is not highly conserved (BP4, BP7). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00484 (87/17976 alleles) in the East Asian population, which is higher than the ClinGen CCDS VCEP’s threshold for BA1 (>0.003), and therefore meets this criterion (BA1). This variant does not appear to have been previously reported in the published literature. It is noted in ClinVar (Variation ID 137434). In summary, this variant meets the criteria to be classified as benign for GAMT deficiency. GAMT-specific ACMG/AMP codes met, as specified by the ClinGen CCDS VCEP (Specifications Version 1.1.0): BA1, BP4, BP7. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022).

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

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 -8.3	GERP -3.1
Overall
CADD	0.881	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.257% East Asian · 113/44,012 alleles

Filtering AF 0.218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.204%

Overall 0.0262% 418/1,594,890 alleles · rare exomes 372/1,442,596 · genomes 46/152,294 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.257%	389
Middle Eastern	0.0828%	1,208
Remaining individualsnot grpmax-eligible	0.0502%	1,992
South Asian	0.025%	4,007
European (non-Finnish)	0.0202%	4,943
Admixed American	0.0087%	11,494
Finnishnot grpmax-eligible	0.0049%	20,393
African / African-American	0.00268%	37,347

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.Asp93=
Coding: c.279C>T
MANE Select: NM_000156
dbSNP: rs144630886
Type: single nucleotide variant
Location: chr19:1399841 (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 93: the rmt2 domain; an α-helix

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.Asp93Val Uncertain significance ★ ⚠ same residue
GAMT p.Asp93Glu Uncertain significance ⚠ same residue
GAMT c.327+43G>A Likely pathogenic ★★★ same condition
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

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-asp93 (accessed [today's date]).

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