Is BCR p.Tyr231= (c.693C>T) pathogenic?

BCR p.Tyr231= (c.693C>T) is classified Likely benign in BCR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-11). Ultra-rare (popmax 0.0262%, nfe).

How common is BCR p.Tyr231= (c.693C>T) in the general population?

BCR p.Tyr231= (c.693C>T) is ultra-rare (popmax 0.0262%, nfe) (gnomAD).

BCR p.Tyr231=

c.693C>T · rs149768123 · VCV734525

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0262%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.45	GERP 0.9, phastCons 0.09
Overall
CADD	6.434	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0262% European (non-Finnish) · 309/1,179,874 alleles

Filtering AF 0.0238% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0228%

Overall 0.0225% 362/1,608,904 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0559%	1,787
European (non-Finnish)grpmax	0.0262%	3,818
Remaining individualsnot grpmax-eligible	0.0192%	5,205
African / African-American	0.00666%	15,012
Admixed American	0.00333%	30,009
South Asian	0.0011%	91,070

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Tyr231=
Coding: c.693C>T
MANE Select: NM_004327
dbSNP: rs149768123
Type: single nucleotide variant
Location: chr22:23181653 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 65.61 · 5 PDB
Residue 231: the 'kinase' region; the 'disordered' region; the 'binding to abl sh2-domain' region

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

Similar variants

BCR p.Tyr231Asn 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-tyr231 (accessed [today's date]).

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