Is TRA2B p.Ser37Cys (c.110C>G) pathogenic?

TRA2B p.Ser37Cys (c.110C>G) is classified Uncertain significance in TRA2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-04). AlphaMissense: likely benign (0.1775); Absent from gnomAD v4.1.

How common is TRA2B p.Ser37Cys (c.110C>G) in the general population?

TRA2B p.Ser37Cys (c.110C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRA2B p.Ser37Cys (c.110C>G)?

AlphaMissense predicts likely benign (score 0.1775) — an in-silico prediction, not a clinical call.

TRA2B p.Ser37Cys

c.110C>G · VCV3901351

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1775 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1775	likely benign
REVEL	0.285	benign-leaning
SaProt	LLR -14.82	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 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 12 kb · p 0.00064 · regional, not allelic
Overall
CADD	28.3	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.Ser37Cys
Coding: c.110C>G
MANE Select: NM_004593
Type: single nucleotide variant
Location: chr3:185926661 (GRCh38)
Gene constraint: LOEUF 0.528 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 57.18 · 4 PDB
Residue 37: 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 p.Thr201Met 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

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-ser37cys (accessed [today's date]).

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