Is AMT p.Glu368Lys (c.1102G>A) pathogenic?

AMT p.Glu368Lys (c.1102G>A) is classified Uncertain significance in AMT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-23). AlphaMissense: likely benign (0.1068); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with AMT p.Glu368Lys (c.1102G>A)?

AMT p.Glu368Lys (c.1102G>A) is associated with Inborn genetic diseases (ClinVar).

How common is AMT p.Glu368Lys (c.1102G>A) in the general population?

AMT p.Glu368Lys (c.1102G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about AMT p.Glu368Lys (c.1102G>A)?

AlphaMissense predicts likely benign (score 0.1068) — an in-silico prediction, not a clinical call.

AMT p.Glu368Lys

c.1102G>A · VCV4576608

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1068 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1068	likely benign
REVEL	0.223	benign-leaning
SaProt	LLR -9.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.68	GERP -0.38, phastCons 0.21
Regional constraint	o/e 0.93	unconstrained · MANE · 4,907 bp · p 0.12 · regional, not allelic
Overall
CADD	15.02	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,898 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00112% 18/1,614,028 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,898
Admixed American	0.00167%	59,986
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.00127%	78,670

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.Glu368Lys
Coding: c.1102G>A
MANE Select: NM_000481
Type: single nucleotide variant
Location: chr3:49417650 (GRCh38)
Gene constraint: LOEUF 0.805 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.66 · 2 PDB
Residue 368: an α-helix

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

Similar variants

AMT p.Glu368Ter Pathogenic ★ same residue
AMT p.Glu368= Likely benign ★ same residue
AMT p.Ala361Val Uncertain significance ★★ ⚠ same condition
AMT p.Arg10Gly Uncertain significance ★★ ⚠ same condition
AMT p.Arg219Cys Uncertain significance ★★ ⚠ same condition
AMT p.Arg297Gln Uncertain significance ★★ ⚠ same condition
AMT p.Arg34Cys Uncertain significance ★★ ⚠ same condition
AMT p.Arg381Gln Uncertain significance ★★ ⚠ 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-glu368lys (accessed [today's date]).

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