Is BSX p.Arg133Leu (c.398G>T) pathogenic?

BSX p.Arg133Leu (c.398G>T) is classified Uncertain significance in BSX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). AlphaMissense: likely pathogenic (0.9892); Absent from gnomAD v4.1.

How common is BSX p.Arg133Leu (c.398G>T) in the general population?

BSX p.Arg133Leu (c.398G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BSX p.Arg133Leu (c.398G>T)?

AlphaMissense predicts likely pathogenic (score 0.9892) — an in-silico prediction, not a clinical call.

BSX p.Arg133Leu

c.398G>T · VCV4646859

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9892 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9892	likely pathogenic
REVEL	0.852	moderately pathogenic-leaning
SaProt	LLR -15.84	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.47, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 2,380 bp · p 0.41 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: BSX
Protein: p.Arg133Leu
Coding: c.398G>T
MANE Select: NM_001098169
Type: single nucleotide variant
Location: chr11:122979322 (GRCh38)
Gene constraint: LOEUF 1.172 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.92
Residue 133: a DNA-binding region

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

Similar variants

BSX p.His231Gln Benign ★★ same type
BSX p.Ser150= Benign ★★ same type
BSX p.Ala66Thr Uncertain significance ★ ⚠ same type
BSX p.Arg190Cys Uncertain significance ★ ⚠ same type
BSX p.Arg48Gln Uncertain significance ★ same type
BSX p.Asp174Asn Uncertain significance ★ ⚠ same type
BSX p.Asp216Tyr Uncertain significance ★ ⚠ same type
BSX p.Asp219Gly 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/bsx-p-arg133leu (accessed [today's date]).

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