Is BROX p.Asn134= (c.402T>C) pathogenic?

BROX p.Asn134= (c.402T>C) is classified Likely benign in BROX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-30). Absent from gnomAD v4.1.

How common is BROX p.Asn134= (c.402T>C) in the general population?

BROX p.Asn134= (c.402T>C) is absent from gnomAD v4.1 (gnomAD).

BROX p.Asn134=

c.402T>C · VCV3993191

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,605,912)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.79	GERP -2, phastCons 1
Overall
CADD	12.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,605,912). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BROX
Protein: p.Asn134=
Coding: c.402T>C
MANE Select: NM_144695
Type: single nucleotide variant
Location: chr1:222724092 (GRCh38)
Gene constraint: LOEUF 1.123 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.15 · 7 PDB
Residue 134: the bro1 domain

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

Similar variants

BROX p.Ala169Val Uncertain significance ★ ⚠ same type
BROX p.Ala191Val Uncertain significance ★ ⚠ same type
BROX p.Ala213Val Uncertain significance ★ ⚠ same type
BROX p.Arg178Gln Uncertain significance ★ ⚠ same type
BROX p.Arg378Lys Uncertain significance ★ ⚠ same type
BROX p.Asn117Ser Uncertain significance ★ ⚠ same type
BROX p.Asn19Ser Uncertain significance ★ ⚠ same type
BROX p.Asn218Ser 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/brox-p-asn134 (accessed [today's date]).

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