Is TST p.Val252Ile (c.754G>A) pathogenic?

TST p.Val252Ile (c.754G>A) is classified Uncertain significance in TST (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.1278); Absent from gnomAD v4.1.

How common is TST p.Val252Ile (c.754G>A) in the general population?

TST p.Val252Ile (c.754G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TST p.Val252Ile (c.754G>A)?

AlphaMissense predicts likely benign (score 0.1278) — an in-silico prediction, not a clinical call.

TST p.Val252Ile

c.754G>A · VCV4192779

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1278 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1278	likely benign
REVEL	0.186	benign-leaning
SaProt	LLR -4.00	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 4.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 7,702 bp · p 0.51 · regional, not allelic
Overall
CADD	20.5	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: TST
Protein: p.Val252Ile
Coding: c.754G>A
MANE Select: NM_003312
Type: single nucleotide variant
Location: chr22:37011167 (GRCh38)
Gene constraint: LOEUF 1.478 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.50 · 1 PDB
Residue 252: the rhodanese 2 domain; a β-strand

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

Similar variants

TST p.Arg132Trp Uncertain significance ★ ⚠ same type
TST p.Arg183Ser Uncertain significance ★ ⚠ same type
TST p.Arg187Leu Uncertain significance ★ ⚠ same type
TST p.Arg206His Uncertain significance ★ ⚠ same type
TST p.Arg230Cys Uncertain significance ★ ⚠ same type
TST p.Arg230His Uncertain significance ★ ⚠ same type
TST p.Arg249Cys Uncertain significance ★ ⚠ same type
TST p.Arg282Gln 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/tst-p-val252ile (accessed [today's date]).

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