Is BCL10 p.Arg232Gln (c.695G>A) pathogenic?

BCL10 p.Arg232Gln (c.695G>A) is classified Uncertain significance in BCL10 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-29). AlphaMissense: likely benign (0.0665); Ultra-rare (popmax 0.0337%, eas); Associated with immunodeficiency 37.

What condition is associated with BCL10 p.Arg232Gln (c.695G>A)?

BCL10 p.Arg232Gln (c.695G>A) is associated with immunodeficiency 37 (ClinVar).

How common is BCL10 p.Arg232Gln (c.695G>A) in the general population?

BCL10 p.Arg232Gln (c.695G>A) is ultra-rare (popmax 0.0337%, eas) (gnomAD).

What do computational predictors say about BCL10 p.Arg232Gln (c.695G>A)?

AlphaMissense predicts likely benign (score 0.0665) — an in-silico prediction, not a clinical call.

BCL10 p.Arg232Gln

c.695G>A · rs547793946 · VCV1471908

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0665 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0337%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 37

Computational evidence

Protein change
AlphaMissense	0.0665	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -6.41	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 -0.24	GERP -4.4
Regional constraint	o/e 0.92	unconstrained · MANE · 349 bp · p 0.37 · regional, not allelic
Overall
CADD	10.14	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 0.0337% East Asian · 15/44,564 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0167%

Overall 0.00317% 50/1,579,312 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0337%	2,971
European (non-Finnish)	0.00292%	34,283
Admixed American	0.00195%	51,396

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: BCL10
Protein: p.Arg232Gln
Coding: c.695G>A
MANE Select: NM_003921
dbSNP: rs547793946
Type: single nucleotide variant
Location: chr1:85267634 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI 0.73 (gnomAD)
Structure: AlphaFold pLDDT 70.43 · 5 PDB
Residue 232: the 'disordered' region

Full BCL10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 37 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BCL10 p.Arg232Ter Uncertain significance ★★ same residue
BCL10 p.Arg87Gln Uncertain significance ★★ ⚠ same condition
BCL10 p.Cys119Tyr Uncertain significance ★★ ⚠ same condition
BCL10 p.Gln97Glu Uncertain significance ★★ ⚠ same condition
BCL10 p.Ile96Val Uncertain significance ★★ ⚠ same condition
BCL10 p.Leu177Ile Uncertain significance ★★ ⚠ same condition
BCL10 p.Thr162Met Uncertain significance ★★ ⚠ same condition
BCL10 p.Thr190Ala Uncertain significance ★★ ⚠ same condition

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/bcl10-p-arg232gln (accessed [today's date]).

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