Is GAMT p.Arg208= (c.624T>C) pathogenic?

GAMT p.Arg208= (c.624T>C) is classified Likely benign in GAMT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-04). Ultra-rare (popmax 0.0165%, mid); Associated with cerebral creatine deficiency syndrome.

What condition is associated with GAMT p.Arg208= (c.624T>C)?

GAMT p.Arg208= (c.624T>C) is associated with cerebral creatine deficiency syndrome (ClinVar).

How common is GAMT p.Arg208= (c.624T>C) in the general population?

GAMT p.Arg208= (c.624T>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

GAMT p.Arg208=

c.624T>C · rs759873807 · VCV1156901

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 0.59	GERP 0.46, phastCons 0.053
Overall
CADD	3.958	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000373% 6/1,610,458 alleles · ultra-rare exomes 6/1,458,144 · genomes 0/152,314 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
South Asian	0.00439%	22,772
European (non-Finnish)	8.48e-05%	1,179,906

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.Arg208=
Coding: c.624T>C
MANE Select: NM_000156
dbSNP: rs759873807
Type: single nucleotide variant
Location: chr19:1397446 (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 208: the rmt2 domain; a UniProt-annotated variant site (in ccds2; retains no significant activity); 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

Similar variants

GAMT p.Arg208Cys Uncertain significance ★★★ ⚠ same residue
GAMT p.Arg208His Uncertain significance ★★★ ⚠ same residue
GAMT p.Arg208Ser Uncertain significance ★★ ⚠ same residue
GAMT p.Arg208Leu Uncertain significance ★ ⚠ same residue
GAMT p.Arg208Pro Likely pathogenic ★★★ same residue
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

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-arg208 (accessed [today's date]).

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