Is TRA2B p.Thr201Met (c.602C>T) pathogenic?

TRA2B p.Thr201Met (c.602C>T) is classified Pathogenic in TRA2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely pathogenic (0.9979); Absent from gnomAD v4.1.

How common is TRA2B p.Thr201Met (c.602C>T) in the general population?

TRA2B p.Thr201Met (c.602C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRA2B p.Thr201Met (c.602C>T)?

AlphaMissense predicts likely pathogenic (score 0.9979) — an in-silico prediction, not a clinical call.

TRA2B p.Thr201Met

c.602C>T · rs2473742811 · VCV2412961

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9979 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9979	likely pathogenic ✓ concordant with ClinVar
REVEL	0.461	indeterminate
SaProt	LLR -14.28	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.13	constrained · MANE · 4,333 bp · p 2.2e-28 · regional, not allelic
Overall
CADD	33.0	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

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: TRA2B
Protein: p.Thr201Met
Coding: c.602C>T
MANE Select: NM_004593
dbSNP: rs2473742811
Type: single nucleotide variant
Location: chr3:185922047 (GRCh38)
Gene constraint: LOEUF 0.528 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 57.18 · 4 PDB
Residue 201: a modified residue (phosphothreonine); the 'linker' region; the 'disordered' region

Full TRA2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRA2B c.170+1G>A Pathogenic ★ same type
TRA2B p.Gln7Ter Pathogenic ★ same type
TRA2B c.171-2A>G Uncertain significance ★ same type
TRA2B c.782+5G>A Uncertain significance ★ same type
TRA2B p.Ala17Pro Uncertain significance ★ ⚠ same type
TRA2B p.Arg74His Uncertain significance ★ ⚠ same type
TRA2B p.Arg82His Uncertain significance ★ ⚠ same type
TRA2B p.Arg91Cys 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/tra2b-p-thr201met (accessed [today's date]).

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