Is GOT1 p.Ala121= (c.363G>A) pathogenic?

GOT1 p.Ala121= (c.363G>A) is classified Benign in GOT1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-23). Common (popmax 25.5%, amr) — too common for a highly-penetrant pathogenic allele; Associated with GOT1-related disorder.

What condition is associated with GOT1 p.Ala121= (c.363G>A)?

GOT1 p.Ala121= (c.363G>A) is associated with GOT1-related disorder (ClinVar).

GOT1 p.Ala121=

Q: How common is GOT1 p.Ala121= (c.363G>A) in the general population?

GOT1 p.Ala121= (c.363G>A) is common (popmax 25.5%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.363G>A · rs2234971 · VCV3060094

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 25.5%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

GOT1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.1	GERP -5.7
Overall
CADD	1.744	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 25.5% Admixed American · 15,304/59,968 alleles

Filtering AF 25.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 25%

Overall 12% 193,533/1,613,078 alleles · common exomes 177,239/1,460,928 · genomes 16,294/152,150 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	25.5%	4
Ashkenazi Jewishnot grpmax-eligible	16.8%	6
East Asian	16%	6
Amishnot grpmax-eligible	12.1%	8
Remaining individualsnot grpmax-eligible	12%	8
European (non-Finnish)	11.9%	8
Finnishnot grpmax-eligible	10.4%	10
South Asian	8.07%	12
Middle Eastern	7.87%	13
African / African-American	4.29%	23

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: GOT1
Protein: p.Ala121=
Coding: c.363G>A
MANE Select: NM_002079
dbSNP: rs2234971
Type: single nucleotide variant
Location: chr10:99406787 (GRCh38)
Structure: AlphaFold pLDDT 88.17

Full GOT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GOT1-related disorder

Similar variants

GOT1 p.Ala121Val Uncertain significance ★ ⚠ same residue
GOT1 p.Arg160His Likely benign ⚠ same condition
GOT1 p.His190= Likely benign same condition
GOT1 c.643-5C>T Benign/Likely benign ★★ same type
GOT1 p.Glu183Gly Benign ★★ ⚠ same type
GOLT1B p.Gly100Asp Uncertain significance ★ ⚠ same type
GOLT1B p.Gly132Ala Uncertain significance ★ ⚠ same type
GOLT1B p.Leu41Ile 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/got1-p-ala121 (accessed [today's date]).

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