Is BCR p.Leu673Phe (c.2019G>C) pathogenic?

BCR p.Leu673Phe (c.2019G>C) is classified Uncertain significance in BCR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-17). AlphaMissense: ambiguous (0.5191); Very rare (popmax 0.00666%, amr).

How common is BCR p.Leu673Phe (c.2019G>C) in the general population?

BCR p.Leu673Phe (c.2019G>C) is very rare (popmax 0.00666%, amr) (gnomAD).

What do computational predictors say about BCR p.Leu673Phe (c.2019G>C)?

AlphaMissense predicts ambiguous (score 0.5191) — an in-silico prediction, not a clinical call.

BCR p.Leu673Phe

c.2019G>C · rs769154760 · VCV2404412

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5191 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Computational evidence

Protein change
AlphaMissense	0.5191	ambiguous
REVEL	0.383	indeterminate
SaProt	LLR -10.44	damaging
Splicing
SpliceAI	Δ0.35	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 2.1	GERP 0.68, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 57 kb · p 4.3e-10 · regional, not allelic
Overall
CADD	27.4	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 0.00666% Admixed American · 4/60,028 alleles

Filtering AF 0.00225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000274% 4/1,461,764 alleles · very rare

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.Leu673Phe
Coding: c.2019G>C
MANE Select: NM_004327
dbSNP: rs769154760
Type: single nucleotide variant
Location: chr22:23273678 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 65.61 · 5 PDB
Residue 673: the dh domain; an α-helix

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-leu673phe (accessed [today's date]).

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