Is TRA2B p.Met1Val (c.1A>G) pathogenic?

TRA2B p.Met1Val (c.1A>G) is classified Pathogenic in TRA2B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-11-25). Absent from gnomAD v4.1; Associated with Ramond-Elliott neurodevelopmental syndrome.

What condition is associated with TRA2B p.Met1Val (c.1A>G)?

TRA2B p.Met1Val (c.1A>G) is associated with Ramond-Elliott neurodevelopmental syndrome (ClinVar).

How common is TRA2B p.Met1Val (c.1A>G) in the general population?

TRA2B p.Met1Val (c.1A>G) is absent from gnomAD v4.1 (gnomAD).

TRA2B p.Met1Val

c.1A>G · VCV4531192

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Ramond-Elliott neurodevelopmental syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function in a LoF-intolerant gene
REVEL	0.33	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.1, phastCons 1
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Met1Val
Coding: c.1A>G
MANE Select: NM_004593
Type: single nucleotide variant
Location: chr3:185937860 (GRCh38)
Gene constraint: LOEUF 0.528 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 57.18 · 4 PDB
Residue 1: the 'disordered' region

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

Disease context

Ramond-Elliott neurodevelopmental syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRA2B p.Met1Arg Pathogenic same residue
TRA2B p.Met1del Pathogenic same residue
TRA2B c.170+1G>A Pathogenic ★ same condition
TRA2B p.Met1fs Uncertain significance ★ same residue
TRA2B c.170+1del Pathogenic same condition
TRA2B p.Gln7Ter Pathogenic ★ same type
TRA2B p.Thr201Met Pathogenic ★ same type
TRA2B c.171-2A>G 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-met1val (accessed [today's date]).

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