Is GAMT p.Phe69= (c.207T>C) pathogenic?

GAMT p.Phe69= (c.207T>C) is classified Likely benign in GAMT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-17). Very rare (popmax 0.00263%, nfe); Associated with cerebral creatine deficiency syndrome.

What condition is associated with GAMT p.Phe69= (c.207T>C)?

GAMT p.Phe69= (c.207T>C) is associated with cerebral creatine deficiency syndrome (ClinVar).

How common is GAMT p.Phe69= (c.207T>C) in the general population?

GAMT p.Phe69= (c.207T>C) is very rare (popmax 0.00263%, nfe) (gnomAD).

GAMT p.Phe69=

c.207T>C · rs1334995399 · VCV1152798

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00263%, nfe)

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 -2.2	GERP -3.1
Overall
CADD	2.618	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00263% European (non-Finnish) · 31/1,178,466 alleles

Filtering AF 0.00189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00199% 32/1,608,666 alleles · very rare exomes 31/1,456,482 · genomes 1/152,184 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00263%	38,015
Admixed American	0.00168%	59,546

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.Phe69=
Coding: c.207T>C
MANE Select: NM_000156
dbSNP: rs1334995399
Type: single nucleotide variant
Location: chr19:1399913 (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 69: the rmt2 domain; a binding site

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 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
GAMT p.Ala75Val 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-phe69 (accessed [today's date]).

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