Is GAMT p.Ser173= (c.519C>T) pathogenic?

GAMT p.Ser173= (c.519C>T) is classified Likely benign in GAMT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). Very rare (popmax 0.00891%, eas); Associated with cerebral creatine deficiency syndrome.

What condition is associated with GAMT p.Ser173= (c.519C>T)?

GAMT p.Ser173= (c.519C>T) is associated with cerebral creatine deficiency syndrome (ClinVar).

How common is GAMT p.Ser173= (c.519C>T) in the general population?

GAMT p.Ser173= (c.519C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

GAMT p.Ser173=

c.519C>T · rs2512224250 · VCV2704489

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00891%, 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 2.3	GERP 0.29, phastCons 1
Overall
CADD	11.19	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,888 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000248% 4/1,613,472 alleles · very rare exomes 4/1,461,140 · genomes 0/152,332 · 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.Ser173=
Coding: c.519C>T
MANE Select: NM_000156
dbSNP: rs2512224250
Type: single nucleotide variant
Location: chr19:1398967 (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 173: 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 p.Ser173Phe Uncertain significance ★ ⚠ same residue
GAMT p.Ser173Thr Uncertain significance ⚠ 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
GAMT c.391+1G>C Pathogenic ★★★ same condition
GAMT c.391+5G>C Likely pathogenic ★★★ same condition
GAMT p.Ala156Asp 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-ser173 (accessed [today's date]).

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