Is AMT p.Val220fs (c.657dup) pathogenic?

AMT p.Val220fs (c.657dup) is classified Pathogenic/Likely pathogenic in AMT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-28). Absent from gnomAD; Associated with glycine encephalopathy.

What condition is associated with AMT p.Val220fs (c.657dup)?

AMT p.Val220fs (c.657dup) is associated with glycine encephalopathy (ClinVar).

How common is AMT p.Val220fs (c.657dup) in the general population?

AMT p.Val220fs (c.657dup) 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.Val220fs

c.657dup · rs2049058298 · VCV1163247

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1

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

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.Val220fs
Coding: c.657dup
MANE Select: NM_000481
dbSNP: rs2049058298
Type: Duplication
Location: chr3:49419298 (GRCh38)
Gene constraint: LOEUF 0.805 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.66 · 2 PDB
Residue 220: 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.Val220Met Uncertain significance ★★ ⚠ same residue
AMT c.1034-1dup Likely pathogenic ★★ same condition
AMT p.Ala21fs Pathogenic ★★ same condition
AMT p.Ala328fs Pathogenic/Likely pathogenic ★★ same condition
AMT p.Leu179fs Pathogenic/Likely pathogenic ★★ same condition
AMT p.Glu150fs Likely pathogenic ★ same condition
AMT p.Glu326delinsGlyValAspValTer Likely pathogenic ★ same condition
AMT p.Ile89fs 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-val220fs (accessed [today's date]).

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