Is GOT2 p.Asp243His (c.727G>C) pathogenic?

GOT2 p.Asp243His (c.727G>C) is classified Uncertain significance in GOT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-06). AlphaMissense: likely pathogenic (0.9991); Absent from gnomAD v4.1.

How common is GOT2 p.Asp243His (c.727G>C) in the general population?

GOT2 p.Asp243His (c.727G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GOT2 p.Asp243His (c.727G>C)?

AlphaMissense predicts likely pathogenic (score 0.9991) — an in-silico prediction, not a clinical call.

GOT2 p.Asp243His

c.727G>C · VCV4030970

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9991 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9991	likely pathogenic · top 1% in GOT2
REVEL	0.847	moderately pathogenic-leaning
SaProt	LLR -16.89	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 26 kb · p 4.2e-08 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: GOT2
Protein: p.Asp243His
Coding: c.727G>C
MANE Select: NM_002080
Type: single nucleotide variant
Location: chr16:58716789 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 94.77 · 3 PDB
Residue 243: a β-strand

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

Similar variants

GOT2 p.Asp243= Likely benign ★ same residue
GOT2 p.Arg262Gly Likely pathogenic ★★ same type
GOT2 p.Gly366Val Likely pathogenic ★★ same type
GOT2 p.Ala89Ser Uncertain significance ★★ ⚠ same type
GOT2 p.Arg325Gln Uncertain significance ★★ ⚠ same type
GOT2 p.Asp190Val Uncertain significance ★★ ⚠ same type
GOT2 p.Asp197Asn Uncertain significance ★★ ⚠ same type
GOT2 p.Gln357Glu Uncertain significance ★★ ⚠ same type

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-asp243his (accessed [today's date]).

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