Is GAMT p.Pro138= (c.414A>G) pathogenic?

GAMT p.Pro138= (c.414A>G) is classified Likely benign in GAMT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-17). Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with GAMT p.Pro138= (c.414A>G)?

GAMT p.Pro138= (c.414A>G) is associated with Inborn genetic diseases, cerebral creatine deficiency syndrome, guanidinoacetate methyltransferase deficiency (ClinVar).

How common is GAMT p.Pro138= (c.414A>G) in the general population?

GAMT p.Pro138= (c.414A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

GAMT p.Pro138=

c.414A>G · rs1376380710 · VCV1152575

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

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 -15	GERP -3
Overall
CADD	0.064	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,924 alleles

Overall 0.000186% 3/1,612,520 alleles · very rare exomes 2/1,461,388 · genomes 1/151,132 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,924
Finnishnot grpmax-eligible	0.00158%	63,434
European (non-Finnish)	8.48e-05%	1,179,752

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.Pro138=
Coding: c.414A>G
MANE Select: NM_000156
dbSNP: rs1376380710
Type: single nucleotide variant
Location: chr19:1399173 (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 138: the rmt2 domain

Full GAMT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cerebral creatine deficiency syndrome guanidinoacetate methyltransferase deficiency

Similar variants

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
GAMT p.Ala156Asp Likely pathogenic ★★★ same condition
GAMT p.Ala54Pro 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-pro138 (accessed [today's date]).

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