Is BCL10 p.Thr91Pro (c.271A>C) pathogenic?

BCL10 p.Thr91Pro (c.271A>C) is classified Uncertain significance in BCL10 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-15). AlphaMissense: likely pathogenic (0.9165); Absent from gnomAD v4.1; Associated with immunodeficiency 37.

What condition is associated with BCL10 p.Thr91Pro (c.271A>C)?

BCL10 p.Thr91Pro (c.271A>C) is associated with immunodeficiency 37 (ClinVar).

How common is BCL10 p.Thr91Pro (c.271A>C) in the general population?

BCL10 p.Thr91Pro (c.271A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCL10 p.Thr91Pro (c.271A>C)?

AlphaMissense predicts likely pathogenic (score 0.9165) — an in-silico prediction, not a clinical call.

BCL10 p.Thr91Pro

c.271A>C · rs1660347523 · VCV854836

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9165 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 37

Computational evidence

Protein change
AlphaMissense	0.9165	likely pathogenic
REVEL	0.266	benign-leaning
SaProt	LLR -9.87	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 8,332 bp · p 5e-10 · regional, not allelic
Overall
CADD	25.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BCL10
Protein: p.Thr91Pro
Coding: c.271A>C
MANE Select: NM_003921
dbSNP: rs1660347523
Type: single nucleotide variant
Location: chr1:85270693 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI 0.73 (gnomAD)
Structure: AlphaFold pLDDT 70.43 · 5 PDB
Residue 91: the card domain; a β-strand

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 condition
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-thr91pro (accessed [today's date]).

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