Is GAMT p.Val67= (c.201G>A) pathogenic?

GAMT p.Val67= (c.201G>A) is classified Likely benign in GAMT (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-27). Ultra-rare (popmax 0.0313%, eas); Associated with cerebral creatine deficiency syndrome.

What condition is associated with GAMT p.Val67= (c.201G>A)?

GAMT p.Val67= (c.201G>A) is associated with cerebral creatine deficiency syndrome, guanidinoacetate methyltransferase deficiency (ClinVar).

How common is GAMT p.Val67= (c.201G>A) in the general population?

GAMT p.Val67= (c.201G>A) is ultra-rare (popmax 0.0313%, eas) (gnomAD).

GAMT p.Val67=

c.201G>A · rs745986528 · VCV700792

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0313%, eas)

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 1.2	GERP 0.3, phastCons 1
Overall
CADD	12.79	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0313% East Asian · 14/44,702 alleles

Filtering AF 0.0189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.000933% 15/1,608,236 alleles · ultra-rare exomes 15/1,455,900 · genomes 0/152,336 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0313%	3,193
Admixed American	0.00168%	59,510

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.Val67=
Coding: c.201G>A
MANE Select: NM_000156
dbSNP: rs745986528
Type: single nucleotide variant
Location: chr19:1399919 (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 67: the rmt2 domain; a β-strand

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

Also linked: guanidinoacetate methyltransferase deficiency

Similar variants

GAMT p.Val67Met Uncertain significance ★★ ⚠ same residue
GAMT p.Val67Glu 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-val67 (accessed [today's date]).

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