Is GOT2 p.Arg68Trp (c.202C>T) pathogenic?

GOT2 p.Arg68Trp (c.202C>T) is classified Conflicting classifications of pathogenicity in GOT2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-11-01). AlphaMissense: likely pathogenic (0.9616); Ultra-rare (popmax 0.0681%, sas).

How common is GOT2 p.Arg68Trp (c.202C>T) in the general population?

GOT2 p.Arg68Trp (c.202C>T) is ultra-rare (popmax 0.0681%, sas) (gnomAD).

What do computational predictors say about GOT2 p.Arg68Trp (c.202C>T)?

AlphaMissense predicts likely pathogenic (score 0.9616) — an in-silico prediction, not a clinical call.

GOT2 p.Arg68Trp

c.202C>T · rs557150117 · VCV1497401

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9616 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0681%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9616	likely pathogenic
REVEL	0.728	pathogenic-leaning
SaProt	LLR -15.70	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 4.4	GERP 1.6, 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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0681% South Asian · 62/91,050 alleles

Filtering AF 0.0545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0495%

Overall 0.00446% 72/1,612,754 alleles · ultra-rare exomes 66/1,460,542 · genomes 6/152,212 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0681%	1,469
East Asian	0.0111%	8,974
Remaining individualsnot grpmax-eligible	0.0032%	31,223
European (non-Finnish)	0.000254%	392,937

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.Arg68Trp
Coding: c.202C>T
MANE Select: NM_002080
dbSNP: rs557150117
Type: single nucleotide variant
Location: chr16:58723790 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 94.77 · 3 PDB

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

Similar variants

GOT2 p.Arg68Gln Uncertain significance ★ ⚠ same residue
GOT2 p.Arg68= 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

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-arg68trp (accessed [today's date]).

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