Is GOT2 p.Ala2Ser (c.4G>T) pathogenic?

GOT2 p.Ala2Ser (c.4G>T) is classified Benign in GOT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.1131); Common (popmax 14%, nfe) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about GOT2 p.Ala2Ser (c.4G>T)?

AlphaMissense predicts likely benign (score 0.1131) — an in-silico prediction, not a clinical call.

GOT2 p.Ala2Ser

Q: How common is GOT2 p.Ala2Ser (c.4G>T) in the general population?

GOT2 p.Ala2Ser (c.4G>T) is common (popmax 14%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4G>T · rs11558171 · VCV1608777

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1131 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 14%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1131	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -8.38	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 4.6	GERP 0.87, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 26 kb · p 4.2e-08 · regional, not allelic
Overall
CADD	20.7	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 14% European (non-Finnish) · 144,367/1,029,510 alleles

Filtering AF 14% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.9%

Overall 12.5% 164,819/1,321,634 alleles · common exomes 151,233/1,169,402 · genomes 13,586/152,232 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	14%	7
Ashkenazi Jewishnot grpmax-eligible	13.9%	7
Finnishnot grpmax-eligible	13.4%	7
Remaining individualsnot grpmax-eligible	11.1%	9
Amishnot grpmax-eligible	8.13%	12
Middle Eastern	7.3%	14
South Asian	6.56%	15
Admixed American	5.27%	19
African / African-American	2.2%	45
East Asian	0.0336%	2,975

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.Ala2Ser
Coding: c.4G>T
MANE Select: NM_002080
dbSNP: rs11558171
Type: single nucleotide variant
Location: chr16:58734225 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 94.77 · 3 PDB
Residue 2: a UniProt-annotated variant site (in)

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

Similar variants

GOT2 p.Ala2= 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
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-ala2ser (accessed [today's date]).

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