Is AMT p.Lys201fs (c.602_603del) pathogenic?

AMT p.Lys201fs (c.602603del) is classified Pathogenic/Likely pathogenic in AMT (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-05-29). Very rare (popmax 0.00659%, sas); Associated with glycine encephalopathy 2.

What condition is associated with AMT p.Lys201fs (c.602_603del)?

AMT p.Lys201fs (c.602_603del) is associated with glycine encephalopathy 2, glycine encephalopathy (ClinVar).

How common is AMT p.Lys201fs (c.602_603del) in the general population?

AMT p.Lys201fs (c.602_603del) is very rare (popmax 0.00659%, sas) (gnomAD).

How is Glycine encephalopathy inherited?

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

AMT p.Lys201fs

c.602_603del · rs1279743247 · VCV1013618

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Conditions

glycine encephalopathy 2

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 1.8	GERP -3.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,088 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00041% 6/1,461,866 alleles · very rare

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.Lys201fs
Coding: c.602_603del
MANE Select: NM_000481
dbSNP: rs1279743247
Type: Deletion
Location: chr3:49419353 (GRCh38)
Gene constraint: LOEUF 0.805 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.66 · 2 PDB
Residue 201: an α-helix

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

Also linked: glycine encephalopathy

For Glycine encephalopathy (Orphanet):

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

Similar variants

AMT c.471+2_471+7del Likely pathogenic ★★ same condition
AMT c.695_696+21del Likely pathogenic ★★ same condition
AMT p.Gly54_Trp55insTer Pathogenic/Likely pathogenic ★★ same condition
AMT p.His75fs Pathogenic/Likely pathogenic ★★ same condition
AMT p.Leu57fs Pathogenic/Likely pathogenic ★★ same condition
AMT p.Met330fs Pathogenic/Likely pathogenic ★★ same condition
AMT p.Pro303fs Pathogenic ★★ same condition
AMT p.Ser353fs 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-lys201fs (accessed [today's date]).

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