Is AMT p.Asp197Asn (c.589G>A) pathogenic?

AMT p.Asp197Asn (c.589G>A) is classified Uncertain significance in AMT (ClinVar, Single submitter, 2 submitters; last evaluated 2023-07-27). AlphaMissense: likely benign (0.0828); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AMT p.Asp197Asn (c.589G>A)?

AMT p.Asp197Asn (c.589G>A) is associated with Inborn genetic diseases, glycine encephalopathy (ClinVar).

How common is AMT p.Asp197Asn (c.589G>A) in the general population?

AMT p.Asp197Asn (c.589G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMT p.Asp197Asn (c.589G>A)?

AlphaMissense predicts likely benign (score 0.0828) — an in-silico prediction, not a clinical call.

AMT p.Asp197Asn

c.589G>A · rs200550585 · VCV991889

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0828 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0828	likely benign
REVEL	0.202	benign-leaning
SaProt	LLR -10.26	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 0.84, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 4,907 bp · p 0.12 · regional, not allelic
Overall
CADD	20.8	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.Asp197Asn
Coding: c.589G>A
MANE Select: NM_000481
dbSNP: rs200550585
Type: single nucleotide variant
Location: chr3:49419367 (GRCh38)
Gene constraint: LOEUF 0.805 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.66 · 2 PDB

Full AMT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: glycine encephalopathy

Similar variants

AMT p.Asp197His Conflicting classifications of pathogenicity ★ ⚠ same residue
AMT p.Asp197= Likely benign ★ same residue
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

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-asp197asn (accessed [today's date]).

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