Is GOT2 p.Glu111Asp (c.333A>C) pathogenic?

GOT2 p.Glu111Asp (c.333A>C) is classified Uncertain significance in GOT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-09). AlphaMissense: likely benign (0.2459); Ultra-rare (popmax 0.0693%, afr).

How common is GOT2 p.Glu111Asp (c.333A>C) in the general population?

GOT2 p.Glu111Asp (c.333A>C) is ultra-rare (popmax 0.0693%, afr) (gnomAD).

What do computational predictors say about GOT2 p.Glu111Asp (c.333A>C)?

AlphaMissense predicts likely benign (score 0.2459) — an in-silico prediction, not a clinical call.

GOT2 p.Glu111Asp

c.333A>C · rs140045671 · VCV2077580

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2459 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0693%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2459	likely benign
REVEL	0.275	benign-leaning
SaProt	LLR -10.54	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6.7	GERP -3.7
Regional constraint	o/e 0.77	unconstrained · MANE · 26 kb · p 4.2e-08 · regional, not allelic
Overall
CADD	13.34	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 0.0693% African / African-American · 52/74,994 alleles

Filtering AF 0.0543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0489%

Overall 0.00347% 56/1,612,446 alleles · ultra-rare exomes 26/1,460,120 · genomes 30/152,326 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0693%	1,442
Admixed American	0.00333%	30,009
Remaining individualsnot grpmax-eligible	0.00321%	31,176

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.Glu111Asp
Coding: c.333A>C
MANE Select: NM_002080
dbSNP: rs140045671
Type: single nucleotide variant
Location: chr16:58722192 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 94.77 · 3 PDB
Residue 111: an α-helix

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

Similar variants

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
GOT2 p.Gln372Arg 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-glu111asp (accessed [today's date]).

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