Is AMT p.Arg320Cys (c.954_958delinsAAGGT) pathogenic?

AMT p.Arg320Cys (c.954958delinsAAGGT) is classified Conflicting classifications of pathogenicity in AMT (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-21). Absent from gnomAD; Associated with glycine encephalopathy.

What condition is associated with AMT p.Arg320Cys (c.954_958delinsAAGGT)?

AMT p.Arg320Cys (c.954_958delinsAAGGT) is associated with glycine encephalopathy (ClinVar).

How common is AMT p.Arg320Cys (c.954_958delinsAAGGT) in the general population?

AMT p.Arg320Cys (c.954_958delinsAAGGT) is absent from gnomAD (gnomAD).

How is Glycine encephalopathy inherited?

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

AMT p.Arg320Cys

c.954_958delinsAAGGT · rs2471146280 · VCV3251505

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 4,907 bp · p 0.12 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AMT
Protein: p.Arg320Cys
Coding: c.954_958delinsAAGGT
MANE Select: NM_000481
dbSNP: rs2471146280
Type: Indel
Location: chr3:49417893 (GRCh38)
Gene constraint: LOEUF 0.805 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.66 · 2 PDB
Residue 320: a UniProt-annotated variant site (in gce2; loss of aminomethyltransferase activity); 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 p.Arg320Gly Likely pathogenic ★★ same residue
AMT p.Arg320His Pathogenic ★★ same residue
AMT p.Arg320Leu Uncertain significance ★★ ⚠ same residue
AMT p.Leu90Pro Uncertain significance ★ same condition
AMT c.1034-1dup Likely pathogenic ★★ same condition
AMT c.339+2T>C Likely pathogenic ★★ same condition
AMT c.471+2_471+7del Likely pathogenic ★★ same condition
AMT c.471+2T>C 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-arg320cys (accessed [today's date]).

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