Is TST p.Arg45Leu (c.134G>T) pathogenic?

TST p.Arg45Leu (c.134G>T) is classified Uncertain significance in TST (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-08). AlphaMissense: likely benign (0.3018); Very rare (popmax 0.00136%, afr).

How common is TST p.Arg45Leu (c.134G>T) in the general population?

TST p.Arg45Leu (c.134G>T) is very rare (popmax 0.00136%, afr) (gnomAD).

What do computational predictors say about TST p.Arg45Leu (c.134G>T)?

AlphaMissense predicts likely benign (score 0.3018) — an in-silico prediction, not a clinical call.

TST p.Arg45Leu

c.134G>T · VCV3811688

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3018 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3018	likely benign
REVEL	0.165	moderately benign-leaning
SaProt	LLR -10.40	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.52	GERP 1.7, phastCons 0.96
Regional constraint	o/e 0.97	unconstrained · MANE · 7,702 bp · p 0.51 · regional, not allelic
Overall
CADD	22.2	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 0.00136% African / African-American · 1/73,756 alleles

Filtering AF 0.000252% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000162%

Overall 0.000512% 8/1,563,626 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00136%	73,756
European (non-Finnish)	0.000606%	164,928

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: TST
Protein: p.Arg45Leu
Coding: c.134G>T
MANE Select: NM_003312
Type: single nucleotide variant
Location: chr22:37018599 (GRCh38)
Gene constraint: LOEUF 1.478 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.50 · 1 PDB
Residue 45: the rhodanese 1 domain; an α-helix

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-arg45leu (accessed [today's date]).

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