Is GOT2 p.Cys272= (c.816C>T) pathogenic?

GOT2 p.Cys272= (c.816C>T) is classified Benign in GOT2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-03). Common (popmax 85.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with developmental and epileptic encephalopathy, 82.

What condition is associated with GOT2 p.Cys272= (c.816C>T)?

GOT2 p.Cys272= (c.816C>T) is associated with developmental and epileptic encephalopathy, 82 (ClinVar).

GOT2 p.Cys272=

Q: How common is GOT2 p.Cys272= (c.816C>T) in the general population?

GOT2 p.Cys272= (c.816C>T) is common (popmax 85.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.816C>T · rs1058192 · VCV1285300

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 85.9%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

developmental and epileptic encephalopathy, 82

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.93	GERP -3.7, phastCons 0.99
Overall
CADD	6.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 85.9% African / African-American · 64,432/74,980 alleles

Filtering AF 85.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 85.1%

Overall 65.1% 1,050,029/1,612,352 alleles · common exomes 941,588/1,460,270 · genomes 108,441/152,082 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	85.9%	1
Middle Eastern	81.1%	1
Ashkenazi Jewishnot grpmax-eligible	76.7%	1
Admixed American	75.9%	1
Remaining individualsnot grpmax-eligible	67.4%	1
European (non-Finnish)	63.2%	2
East Asian	63.1%	2
Amishnot grpmax-eligible	62.9%	2
Finnishnot grpmax-eligible	62.6%	2
South Asian	61.8%	2

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.Cys272=
Coding: c.816C>T
MANE Select: NM_002080
dbSNP: rs1058192
Type: single nucleotide variant
Location: chr16:58716700 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 94.77 · 3 PDB
Residue 272: a β-strand

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

Disease context

developmental and epileptic encephalopathy, 82 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GOT2 p.Arg262Gly Likely pathogenic ★★ same condition
GOT2 p.Gly366Val 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

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-cys272 (accessed [today's date]).

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