Is GOT2 p.Arg303Lys (c.908G>A) pathogenic?

GOT2 p.Arg303Lys (c.908G>A) is classified Uncertain significance in GOT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-05). AlphaMissense: likely benign (0.3289); Very rare (popmax 0.00534%, afr).

How common is GOT2 p.Arg303Lys (c.908G>A) in the general population?

GOT2 p.Arg303Lys (c.908G>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about GOT2 p.Arg303Lys (c.908G>A)?

AlphaMissense predicts likely benign (score 0.3289) — an in-silico prediction, not a clinical call.

GOT2 p.Arg303Lys

c.908G>A · rs371259097 · VCV2420473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3289 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3289	likely benign
REVEL	0.5	indeterminate
SaProt	LLR -9.99	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.61	donor gain · deltas
Pangolin	Δ0.47	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.8	GERP 0.86, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 26 kb · p 4.2e-08 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00534% African / African-American · 4/74,908 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00192% 31/1,613,930 alleles · very rare exomes 24/1,461,768 · genomes 7/152,162 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,727
European (non-Finnish)	0.00229%	43,703

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.Arg303Lys
Coding: c.908G>A
MANE Select: NM_002080
dbSNP: rs371259097
Type: single nucleotide variant
Location: chr16:58716125 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 94.77 · 3 PDB
Residue 303: 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-arg303lys (accessed [today's date]).

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