Is BCR p.Ser504Leu (c.1511C>T) pathogenic?

BCR p.Ser504Leu (c.1511C>T) is classified Uncertain significance in BCR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely benign (0.2593); Very rare (popmax 0.0022%, sas).

How common is BCR p.Ser504Leu (c.1511C>T) in the general population?

BCR p.Ser504Leu (c.1511C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about BCR p.Ser504Leu (c.1511C>T)?

AlphaMissense predicts likely benign (score 0.2593) — an in-silico prediction, not a clinical call.

BCR p.Ser504Leu

c.1511C>T · VCV3991174

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2593 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2593	likely benign
REVEL	0.576	indeterminate
SaProt	LLR -13.22	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 57 kb · p 4.3e-10 · regional, not allelic
Overall
CADD	34.0	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 0.0022% South Asian · 2/91,058 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00137% 20/1,461,680 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,529
European (non-Finnish)	0.00153%	65,555

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.Ser504Leu
Coding: c.1511C>T
MANE Select: NM_004327
Type: single nucleotide variant
Location: chr22:23260999 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 65.61 · 5 PDB
Residue 504: 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-ser504leu (accessed [today's date]).

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