Is TRA2B p.Ala17Pro (c.49G>C) pathogenic?

TRA2B p.Ala17Pro (c.49G>C) is classified Uncertain significance in TRA2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-20). AlphaMissense: likely benign (0.1008); Very rare (popmax 0.00667%, amr); Associated with Inborn genetic diseases.

What condition is associated with TRA2B p.Ala17Pro (c.49G>C)?

TRA2B p.Ala17Pro (c.49G>C) is associated with Inborn genetic diseases (ClinVar).

How common is TRA2B p.Ala17Pro (c.49G>C) in the general population?

TRA2B p.Ala17Pro (c.49G>C) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about TRA2B p.Ala17Pro (c.49G>C)?

AlphaMissense predicts likely benign (score 0.1008) — an in-silico prediction, not a clinical call.

TRA2B p.Ala17Pro

c.49G>C · VCV3460644

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1008 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1008	likely benign
REVEL	0.208	benign-leaning
SaProt	LLR -5.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.42	acceptor gain · deltas
Pangolin	Δ0.28	gain · loss 0.12 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 12 kb · p 0.00064 · regional, not allelic
Overall
CADD	29.4	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 0.00667% Admixed American · 4/60,012 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000248% 4/1,614,052 alleles · very rare exomes 4/1,461,788 · genomes 0/152,264 · joint denominator

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.Ala17Pro
Coding: c.49G>C
MANE Select: NM_004593
Type: single nucleotide variant
Location: chr3:185926722 (GRCh38)
Gene constraint: LOEUF 0.528 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 57.18 · 4 PDB
Residue 17: 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.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
TRA2B p.Ser270Thr 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-ala17pro (accessed [today's date]).

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