Is GSTA2 p.Ser18Pro (c.52T>C) pathogenic?

GSTA2 p.Ser18Pro (c.52T>C) is classified Uncertain significance in GSTA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: likely benign (0.1624); Very rare (popmax 8.48e-05%, nfe).

How common is GSTA2 p.Ser18Pro (c.52T>C) in the general population?

GSTA2 p.Ser18Pro (c.52T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about GSTA2 p.Ser18Pro (c.52T>C)?

AlphaMissense predicts likely benign (score 0.1624) — an in-silico prediction, not a clinical call.

GSTA2 p.Ser18Pro

c.52T>C · VCV4674228

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1624 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1624	likely benign
REVEL	0.122	moderately benign-leaning
SaProt	LLR -6.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.5	GERP -3.7
Regional constraint	o/e 1.16	unconstrained · MANE · 7,367 bp · p 0.0095 · regional, not allelic
Overall
CADD	5.429	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 8.48e-05% European (non-Finnish) · 1/1,179,716 alleles

Overall 6.2e-05% 1/1,613,634 alleles · very rare exomes 1/1,461,458 · genomes 0/152,176 · joint denominator

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: GSTA2
Protein: p.Ser18Pro
Coding: c.52T>C
MANE Select: NM_000846
Type: single nucleotide variant
Location: chr6:52757896 (GRCh38)
Gene constraint: LOEUF 1.635 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.70 · 4 PDB
Residue 18: the gst n-terminal domain; an α-helix

Full GSTA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GSTA2 p.Ala100Val Uncertain significance ★ ⚠ same type
GSTA2 p.Ala156Val Uncertain significance ★ ⚠ same type
GSTA2 p.Asn130Asp Uncertain significance ★ ⚠ same type
GSTA2 p.Asp118Gly Uncertain significance ★ ⚠ same type
GSTA2 p.Glu168Ala Uncertain significance ★ ⚠ same type
GSTA2 p.Gly150Val Uncertain significance ★ ⚠ same type
GSTA2 p.Ile60Asn Uncertain significance ★ ⚠ same type
GSTA2 p.Leu107Pro 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/gsta2-p-ser18pro (accessed [today's date]).

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