Is BCR p.Arg132Pro (c.395G>C) pathogenic?

BCR p.Arg132Pro (c.395G>C) is classified Likely benign in BCR (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-10). AlphaMissense: likely benign (0.113); Rare (popmax 0.144%, nfe).

How common is BCR p.Arg132Pro (c.395G>C) in the general population?

BCR p.Arg132Pro (c.395G>C) is rare (popmax 0.144%, nfe) (gnomAD).

What do computational predictors say about BCR p.Arg132Pro (c.395G>C)?

AlphaMissense predicts likely benign (score 0.113) — an in-silico prediction, not a clinical call.

BCR p.Arg132Pro

c.395G>C · rs200084105 · VCV725929

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.113 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.144%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.113	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -5.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP -0.32, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 73 kb · p 1.1e-11 · regional, not allelic
Overall
CADD	17.97	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

Grpmax group 0.144% European (non-Finnish) · 1,632/1,134,426 alleles

Filtering AF 0.138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.136%

Overall 0.114% 1,710/1,505,872 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.144%	695
Remaining individualsnot grpmax-eligible	0.0881%	1,134
Middle Eastern	0.0202%	4,960
African / African-American	0.0184%	5,436
Finnishnot grpmax-eligible	0.0119%	8,370
Admixed American	0.0112%	8,918
South Asian	0.00262%	38,103

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: BCR
Protein: p.Arg132Pro
Coding: c.395G>C
MANE Select: NM_004327
dbSNP: rs200084105
Type: single nucleotide variant
Location: chr22:23181355 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 65.61 · 5 PDB
Residue 132: the 'kinase' region; the 'disordered' region

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

Similar variants

BCR p.Arg132Leu Uncertain significance ★ ⚠ same residue
BCR p.Ser356Arg Uncertain significance ★★ ⚠ same type
BCR c.2116-6C>G Benign/Likely benign ★★ same type
BCR c.2116-7C>A Benign/Likely benign ★★ same type
BCR c.2526+7G>T Benign/Likely benign ★★ same type
BCR c.3073-8T>C Benign ★★ same type
BCR c.3183-4G>A Benign ★★ same type
BCR p.Ala1257= Benign/Likely benign ★★ 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/bcr-p-arg132pro (accessed [today's date]).

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