Is AMT p.Met1Ile (c.3G>A) pathogenic?

AMT p.Met1Ile (c.3G>A) is classified Likely pathogenic in AMT (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-22). Absent from gnomAD v4.1; Associated with glycine encephalopathy 2.

What condition is associated with AMT p.Met1Ile (c.3G>A)?

AMT p.Met1Ile (c.3G>A) is associated with glycine encephalopathy 2 (ClinVar).

How common is AMT p.Met1Ile (c.3G>A) in the general population?

AMT p.Met1Ile (c.3G>A) is absent from gnomAD v4.1 (gnomAD).

How is Glycine encephalopathy inherited?

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

AMT p.Met1Ile

c.3G>A · rs2107938475 · VCV1323888

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

glycine encephalopathy 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.525	indeterminate
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.2	GERP 2.2, phastCons 1
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AMT
Protein: p.Met1Ile
Coding: c.3G>A
MANE Select: NM_032316 · reported on NM_000481
dbSNP: rs2107938475
Type: single nucleotide variant
Location: chr3:49422448 (GRCh38)

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

Disease context

glycine encephalopathy 2 — 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)

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-met1ile (accessed [today's date]).

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