Is GOT2 p.Arg350His (c.1049G>A) pathogenic?

GOT2 p.Arg350His (c.1049G>A) is classified Uncertain significance in GOT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-05). AlphaMissense: likely pathogenic (0.8769); Ultra-rare (popmax 0.0147%, afr).

How common is GOT2 p.Arg350His (c.1049G>A) in the general population?

GOT2 p.Arg350His (c.1049G>A) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

What do computational predictors say about GOT2 p.Arg350His (c.1049G>A)?

AlphaMissense predicts likely pathogenic (score 0.8769) — an in-silico prediction, not a clinical call.

GOT2 p.Arg350His

c.1049G>A · rs148828634 · VCV2593725

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8769 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8769	likely pathogenic
REVEL	0.932	strongly pathogenic-leaning
SaProt	LLR -14.49	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 4.1	GERP 1.7, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 26 kb · p 4.2e-08 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.0147% African / African-American · 11/74,892 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.00174% 28/1,612,170 alleles · ultra-rare exomes 20/1,460,038 · genomes 8/152,132 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,808
South Asian	0.0022%	45,509
Admixed American	0.00167%	59,980
Finnishnot grpmax-eligible	0.00156%	64,004
European (non-Finnish)	0.0011%	90,653

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.Arg350His
Coding: c.1049G>A
MANE Select: NM_002080
dbSNP: rs148828634
Type: single nucleotide variant
Location: chr16:58709538 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 94.77 · 3 PDB
Residue 350: an α-helix

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

Similar variants

GOT2 p.Arg350Cys Uncertain significance ★ ⚠ 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-arg350his (accessed [today's date]).

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