Is GOT2 p.Gly366Val (c.1097G>T) pathogenic?

GOT2 p.Gly366Val (c.1097G>T) is classified Likely pathogenic in GOT2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2020-05-29). AlphaMissense: likely pathogenic (0.6579); Very rare (popmax 8.48e-05%, nfe); Associated with developmental and epileptic encephalopathy.

What condition is associated with GOT2 p.Gly366Val (c.1097G>T)?

GOT2 p.Gly366Val (c.1097G>T) is associated with developmental and epileptic encephalopathy, developmental and epileptic encephalopathy, 82 (ClinVar).

How common is GOT2 p.Gly366Val (c.1097G>T) in the general population?

GOT2 p.Gly366Val (c.1097G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Non-specific syndromic intellectual disability inherited?

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

What do computational predictors say about GOT2 p.Gly366Val (c.1097G>T)?

AlphaMissense predicts likely pathogenic (score 0.6579) — an in-silico prediction, not a clinical call.

GOT2 p.Gly366Val

c.1097G>T · rs1597696047 · VCV691281

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6579 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy

Computational evidence

Protein change
AlphaMissense	0.6579	likely pathogenic ✓ concordant with ClinVar
REVEL	0.917	moderately pathogenic-leaning
SaProt	LLR -14.08	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.85, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 26 kb · p 4.2e-08 · regional, not allelic
Overall
CADD	26.2	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 8.48e-05% European (non-Finnish) · 1/1,179,786 alleles

Overall 6.2e-05% 1/1,613,912 alleles · very rare exomes 1/1,461,588 · genomes 0/152,324 · joint denominator

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: GOT2
Protein: p.Gly366Val
Coding: c.1097G>T
MANE Select: NM_002080
dbSNP: rs1597696047
Type: single nucleotide variant
Location: chr16:58709490 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 94.77 · 3 PDB
Residue 366: a UniProt-annotated variant site (in dee82; uncertain significance; decreased glutamate oxaloacetate transferase activity)

Full GOT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 82

For Non-specific syndromic intellectual disability (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Childhood, Infancy

Similar variants

GOT2 p.Arg262Gly Likely pathogenic ★★ same condition
GOT2 p.Ala89Ser Uncertain significance ★★ ⚠ same condition
GOT2 p.Asp190Val Uncertain significance ★★ ⚠ same condition
GOT2 p.Asp197Asn Uncertain significance ★★ ⚠ same condition
GOT2 p.Leu362Phe Uncertain significance ★★ ⚠ same condition
GOT2 p.Pro78Leu Uncertain significance ★★ ⚠ same condition
GOT2 p.Val294Leu Uncertain significance ★★ same condition
GOT2 p.Asn71= Benign ★★ 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/got2-p-gly366val (accessed [today's date]).

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