Is AMT p.Lys358del (c.1068GAA[2]) pathogenic?

AMT p.Lys358del (c.1068GAA[2]) is classified Conflicting classifications of pathogenicity in AMT (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2022-06-10). Very rare (popmax 0.00333%, amr); Associated with glycine encephalopathy.

What condition is associated with AMT p.Lys358del (c.1068GAA[2])?

AMT p.Lys358del (c.1068GAA[2]) is associated with glycine encephalopathy, glycine encephalopathy 1 (ClinVar).

How common is AMT p.Lys358del (c.1068GAA[2]) in the general population?

AMT p.Lys358del (c.1068GAA[2]) is very rare (popmax 0.00333%, amr) (gnomAD).

How is Glycine encephalopathy inherited?

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

AMT p.Lys358del

c.1068GAA[2] · rs768940499 · VCV1687275

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

glycine encephalopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.1	GERP -4

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,992 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00041% 6/1,461,832 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,996
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)	0.000254%	393,343

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.Lys358del
Coding: c.1068GAA[2]
MANE Select: NM_000481
dbSNP: rs768940499
Type: Microsatellite
Location: chr3:49417676 (GRCh38)
Gene constraint: LOEUF 0.805 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.66 · 2 PDB
Residue 358: 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

Also linked: glycine encephalopathy 1

For Glycine encephalopathy (Orphanet):

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

Similar variants

AMT p.Lys358Thr Uncertain significance ★ ⚠ same residue
AMT p.Met84fs Pathogenic/Likely pathogenic ★★ same condition
AMT p.Gln385del Uncertain significance ★★ same condition
AMT c.471+12_471+13del Benign/Likely benign ★★ same condition
AMT p.Arg73fs Likely pathogenic ★ same condition
AMT p.His333fs Pathogenic ★ same condition
AMT p.Leu356fs Likely pathogenic ★ same condition
AMT p.Ser216fs 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-lys358del (accessed [today's date]).

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