Is TRA2B p.Ser270Thr (c.809G>C) pathogenic?

TRA2B p.Ser270Thr (c.809G>C) is classified Uncertain significance in TRA2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: likely benign (0.3057); Ultra-rare (popmax 0.0286%, sas); Associated with Inborn genetic diseases.

What condition is associated with TRA2B p.Ser270Thr (c.809G>C)?

TRA2B p.Ser270Thr (c.809G>C) is associated with Inborn genetic diseases (ClinVar).

How common is TRA2B p.Ser270Thr (c.809G>C) in the general population?

TRA2B p.Ser270Thr (c.809G>C) is ultra-rare (popmax 0.0286%, sas) (gnomAD).

What do computational predictors say about TRA2B p.Ser270Thr (c.809G>C)?

AlphaMissense predicts likely benign (score 0.3057) — an in-silico prediction, not a clinical call.

TRA2B p.Ser270Thr

c.809G>C · VCV4189711

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3057 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0286%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3057	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -9.10	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 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 1,736 bp · p 0.015 · regional, not allelic
Overall
CADD	24.9	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 0.0286% South Asian · 26/91,038 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.00174% 28/1,613,596 alleles · ultra-rare exomes 27/1,461,442 · genomes 1/152,154 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0286%	3,501
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0016%	62,476

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: TRA2B
Protein: p.Ser270Thr
Coding: c.809G>C
MANE Select: NM_004593
Type: single nucleotide variant
Location: chr3:185918412 (GRCh38)
Gene constraint: LOEUF 0.528 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 57.18 · 4 PDB
Residue 270: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRA2B p.Ala17Pro Uncertain significance ★ ⚠ same condition
TRA2B p.Arg74His Uncertain significance ★ ⚠ same condition
TRA2B p.Arg82His Uncertain significance ★ ⚠ same condition
TRA2B p.Arg91Cys Uncertain significance ★ ⚠ same condition
TRA2B p.Asn8Thr Uncertain significance ★ ⚠ same condition
TRA2B p.Asp146Asn Uncertain significance ★ same condition
TRA2B p.Asp257Glu Uncertain significance ★ ⚠ same condition
TRA2B p.His98Arg Uncertain significance ★ ⚠ same condition

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-ser270thr (accessed [today's date]).

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