Is AMT p.Gly293= (c.879G>C) pathogenic?

AMT p.Gly293= (c.879G>C) is classified Likely benign in AMT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-01). Ultra-rare (popmax 0.0172%, mid); Associated with glycine encephalopathy.

What condition is associated with AMT p.Gly293= (c.879G>C)?

AMT p.Gly293= (c.879G>C) is associated with glycine encephalopathy (ClinVar).

How common is AMT p.Gly293= (c.879G>C) in the general population?

AMT p.Gly293= (c.879G>C) is ultra-rare (popmax 0.0172%, mid) (gnomAD).

How is Glycine encephalopathy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AMT p.Gly293=

c.879G>C · rs972670254 · VCV1114280

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0172%, mid)

Conditions

glycine encephalopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.013	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1	GERP -4.2, phastCons 0.002
Overall
CADD	5.187	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0172% Middle Eastern · 1/5,814 alleles

Overall 0.000343% 5/1,455,946 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0172%	5,814
Remaining individualsnot grpmax-eligible	0.00642%	15,570

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: AMT
Protein: p.Gly293=
Coding: c.879G>C
MANE Select: NM_000481
dbSNP: rs972670254
Type: single nucleotide variant
Location: chr3:49417972 (GRCh38)
Gene constraint: LOEUF 0.805 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.66 · 2 PDB

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

Disease context

glycine encephalopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycine encephalopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

AMT p.Gly293Glu Uncertain significance ★★ ⚠ same residue
AMT c.339+2T>C Likely pathogenic ★★ same condition
AMT c.471+2T>C Pathogenic ★★ same condition
AMT c.697-1G>A Likely pathogenic ★★ same condition
AMT c.878-1G>A Pathogenic ★★ same condition
AMT c.91-2A>G Likely pathogenic ★★ same condition
AMT c.-58C>T Pathogenic/Likely pathogenic ★★ same condition
AMT p.Arg222Cys 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/amt-p-gly293 (accessed [today's date]).

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