Is AMT p.Ile344Phe (c.1030A>T) pathogenic?

AMT p.Ile344Phe (c.1030A>T) is classified Uncertain significance in AMT (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-16). AlphaMissense: ambiguous (0.5243); Absent from gnomAD v4.1; Associated with glycine encephalopathy.

What condition is associated with AMT p.Ile344Phe (c.1030A>T)?

AMT p.Ile344Phe (c.1030A>T) is associated with glycine encephalopathy (ClinVar).

How common is AMT p.Ile344Phe (c.1030A>T) in the general population?

AMT p.Ile344Phe (c.1030A>T) 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.

What do computational predictors say about AMT p.Ile344Phe (c.1030A>T)?

AlphaMissense predicts ambiguous (score 0.5243) — an in-silico prediction, not a clinical call.

AMT p.Ile344Phe

c.1030A>T · rs2049024917 · VCV966575

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5243 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

glycine encephalopathy

Computational evidence

Protein change
AlphaMissense	0.5243	ambiguous
REVEL	0.774	moderately pathogenic-leaning
SaProt	LLR -13.45	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.89 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.2	GERP 1.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 4,907 bp · p 0.12 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ile344Phe
Coding: c.1030A>T
MANE Select: NM_000481
dbSNP: rs2049024917
Type: single nucleotide variant
Location: chr3:49417821 (GRCh38)
Gene constraint: LOEUF 0.805 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.66 · 2 PDB
Residue 344: a β-strand

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 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
AMT p.Arg265Cys Pathogenic/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/amt-p-ile344phe (accessed [today's date]).

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