Is BCR p.Arg78Trp (c.232C>T) pathogenic?

BCR p.Arg78Trp (c.232C>T) is classified Uncertain significance in BCR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-03). AlphaMissense: ambiguous (0.3971); Very rare (popmax 0.00779%, nfe).

How common is BCR p.Arg78Trp (c.232C>T) in the general population?

BCR p.Arg78Trp (c.232C>T) is very rare (popmax 0.00779%, nfe) (gnomAD).

What do computational predictors say about BCR p.Arg78Trp (c.232C>T)?

AlphaMissense predicts ambiguous (score 0.3971) — an in-silico prediction, not a clinical call.

BCR p.Arg78Trp

c.232C>T · rs761816882 · VCV2368133

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3971 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00779%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3971	ambiguous
REVEL	0.181	moderately benign-leaning
SaProt	LLR -8.70	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP -3.5, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 73 kb · p 1.1e-11 · regional, not allelic
Overall
CADD	21.9	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 0.00779% European (non-Finnish) · 79/1,014,436 alleles

Filtering AF 0.00635% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00588%

Overall 0.00716% 84/1,173,180 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00779%	12,841
Admixed American	0.00547%	18,274
Remaining individualsnot grpmax-eligible	0.00422%	23,697
African / African-American	0.00152%	65,858

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.Arg78Trp
Coding: c.232C>T
MANE Select: NM_004327
dbSNP: rs761816882
Type: single nucleotide variant
Location: chr22:23181192 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 65.61 · 5 PDB
Residue 78: the 'kinase' region; the 'disordered' region

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

Similar variants

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
BCR p.Ala152Val 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-arg78trp (accessed [today's date]).

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