Is BCR p.Ser235Phe (c.704C>T) pathogenic?

BCR p.Ser235Phe (c.704C>T) is classified Uncertain significance in BCR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-25). AlphaMissense: likely benign (0.1163); Very rare (popmax 0.00666%, amr).

How common is BCR p.Ser235Phe (c.704C>T) in the general population?

BCR p.Ser235Phe (c.704C>T) is very rare (popmax 0.00666%, amr) (gnomAD).

What do computational predictors say about BCR p.Ser235Phe (c.704C>T)?

AlphaMissense predicts likely benign (score 0.1163) — an in-silico prediction, not a clinical call.

BCR p.Ser235Phe

c.704C>T · VCV3260718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1163 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1163	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -8.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -0.16, phastCons 0.018
Regional constraint	o/e 1.27	unconstrained · MANE · 73 kb · p 1.1e-11 · regional, not allelic
Overall
CADD	16.23	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00666% Admixed American · 4/60,016 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00124% 20/1,607,654 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00666%	15,004
African / African-American	0.00666%	15,012
Remaining individualsnot grpmax-eligible	0.0048%	20,814
South Asian	0.00439%	22,766
European (non-Finnish)	0.000339%	294,953

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.Ser235Phe
Coding: c.704C>T
MANE Select: NM_004327
Type: single nucleotide variant
Location: chr22:23181664 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 65.61 · 5 PDB
Residue 235: 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.Ser235= Likely benign ★ 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-ser235phe (accessed [today's date]).

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