Is AMT p.Glu379Ala (c.1136A>C) pathogenic?

AMT p.Glu379Ala (c.1136A>C) is classified Uncertain significance in AMT (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-09-08). AlphaMissense: likely benign (0.203); Ultra-rare (popmax 0.0349%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AMT p.Glu379Ala (c.1136A>C)?

AMT p.Glu379Ala (c.1136A>C) is associated with Inborn genetic diseases, glycine encephalopathy (ClinVar).

How common is AMT p.Glu379Ala (c.1136A>C) in the general population?

AMT p.Glu379Ala (c.1136A>C) is ultra-rare (popmax 0.0349%, nfe) (gnomAD).

What do computational predictors say about AMT p.Glu379Ala (c.1136A>C)?

AlphaMissense predicts likely benign (score 0.203) — an in-silico prediction, not a clinical call.

AMT p.Glu379Ala

c.1136A>C · rs201189946 · VCV900804

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.203 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0349%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.203	likely benign
REVEL	0.777	moderately pathogenic-leaning
SaProt	LLR -11.74	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 4,907 bp · p 0.12 · regional, not allelic
Overall
CADD	28.3	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

Grpmax group 0.0349% European (non-Finnish) · 412/1,180,040 alleles

Filtering AF 0.0321% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.031%

Overall 0.0273% 441/1,614,024 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0349%	2,864
Finnishnot grpmax-eligible	0.0219%	4,573
Remaining individualsnot grpmax-eligible	0.0192%	5,207
African / African-American	0.00267%	37,446
Admixed American	0.00167%	59,996

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.Glu379Ala
Coding: c.1136A>C
MANE Select: NM_000481
dbSNP: rs201189946
Type: single nucleotide variant
Location: chr3:49417616 (GRCh38)
Gene constraint: LOEUF 0.805 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.66 · 2 PDB
Residue 379: a β-strand

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 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
AMT p.Arg222Cys Pathogenic ★★ same condition
AMT p.Arg265Cys 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-glu379ala (accessed [today's date]).

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