Is GOT1 p.Ser138Ala (c.412T>G) pathogenic?

GOT1 p.Ser138Ala (c.412T>G) is classified Uncertain significance in GOT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely benign (0.0799); Absent from gnomAD v4.1.

How common is GOT1 p.Ser138Ala (c.412T>G) in the general population?

GOT1 p.Ser138Ala (c.412T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GOT1 p.Ser138Ala (c.412T>G)?

AlphaMissense predicts likely benign (score 0.0799) — an in-silico prediction, not a clinical call.

GOT1 p.Ser138Ala

c.412T>G · VCV4672765

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0799 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0799	likely benign
REVEL	0.274	benign-leaning
SaProt	LLR -7.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 1.7, phastCons 1
Overall
CADD	18.18	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GOT1
Protein: p.Ser138Ala
Coding: c.412T>G
MANE Select: NM_002079
Type: single nucleotide variant
Location: chr10:99406738 (GRCh38)
Structure: AlphaFold pLDDT 88.17

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

Similar variants

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
GOLT1B p.Lys64Asn Uncertain significance ★ ⚠ same type
GOLT1B p.Phe56Cys Uncertain significance ★ ⚠ same type
GOLT1B p.Pro83Leu 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-ser138ala (accessed [today's date]).

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