Is GAMT p.Pro82= (c.246C>T) pathogenic?

GAMT p.Pro82= (c.246C>T) is classified Likely benign in GAMT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-07). Very rare (popmax 0.00112%, sas); Associated with cerebral creatine deficiency syndrome.

What condition is associated with GAMT p.Pro82= (c.246C>T)?

GAMT p.Pro82= (c.246C>T) is associated with cerebral creatine deficiency syndrome (ClinVar).

How common is GAMT p.Pro82= (c.246C>T) in the general population?

GAMT p.Pro82= (c.246C>T) is very rare (popmax 0.00112%, sas) (gnomAD).

GAMT p.Pro82=

c.246C>T · rs2512226405 · VCV2012879

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00112%, sas)

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 2.9	GERP 0.37, phastCons 1
Overall
CADD	7.448	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00112% South Asian · 1/89,464 alleles

Overall 0.000125% 2/1,605,580 alleles · very rare exomes 2/1,453,274 · genomes 0/152,306 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00112%	89,464
European (non-Finnish)	8.5e-05%	1,176,831

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.Pro82=
Coding: c.246C>T
MANE Select: NM_000156
dbSNP: rs2512226405
Type: single nucleotide variant
Location: chr19:1399874 (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 82: the rmt2 domain

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.Pro82Ser 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
GAMT p.Ala74Pro 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-pro82 (accessed [today's date]).

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