Is TST p.Val152Phe (c.454G>T) pathogenic?

TST p.Val152Phe (c.454G>T) is classified Uncertain significance in TST (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-11). AlphaMissense: likely benign (0.1344); Rare (popmax 0.169%, eas).

How common is TST p.Val152Phe (c.454G>T) in the general population?

TST p.Val152Phe (c.454G>T) is rare (popmax 0.169%, eas) (gnomAD).

What do computational predictors say about TST p.Val152Phe (c.454G>T)?

AlphaMissense predicts likely benign (score 0.1344) — an in-silico prediction, not a clinical call.

TST p.Val152Phe

c.454G>T · rs759704785 · VCV2599334

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1344 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.169%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1344	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -9.88	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 -2.6	GERP -3.4
Regional constraint	o/e 0.97	unconstrained · MANE · 7,702 bp · p 0.51 · regional, not allelic
Overall
CADD	5.657	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 0.169% East Asian · 76/44,886 alleles

Filtering AF 0.139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.127%

Overall 0.00471% 76/1,614,108 alleles · rare

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.Val152Phe
Coding: c.454G>T
MANE Select: NM_003312
dbSNP: rs759704785
Type: single nucleotide variant
Location: chr22:37018279 (GRCh38)
Gene constraint: LOEUF 1.478 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.50 · 1 PDB
Residue 152: the 'hinge' region

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-val152phe (accessed [today's date]).

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