Is BCR p.Val1243Asp (c.3728T>A) pathogenic?

BCR p.Val1243Asp (c.3728T>A) is classified Uncertain significance in BCR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-19). AlphaMissense: likely pathogenic (0.994); Very rare (popmax 0.00167%, amr).

How common is BCR p.Val1243Asp (c.3728T>A) in the general population?

BCR p.Val1243Asp (c.3728T>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about BCR p.Val1243Asp (c.3728T>A)?

AlphaMissense predicts likely pathogenic (score 0.994) — an in-silico prediction, not a clinical call.

BCR p.Val1243Asp

c.3728T>A · rs2074059419 · VCV2336462

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.994 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.994	likely pathogenic · top 7% in BCR
REVEL	0.643	indeterminate
SaProt	LLR -14.60	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 3,709 bp · p 0.001 · regional, not allelic
Overall
CADD	32.0	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

Grpmax group 0.00167% Admixed American · 1/60,024 alleles

Overall 0.000137% 2/1,461,280 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,024
European (non-Finnish)	8.48e-05%	1,179,901

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.Val1243Asp
Coding: c.3728T>A
MANE Select: NM_004327
dbSNP: rs2074059419
Type: single nucleotide variant
Location: chr22:23315434 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 65.61 · 5 PDB
Residue 1243: the rho-gap domain

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-val1243asp (accessed [today's date]).

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