Is BCL10 p.Pro193Leu (c.578C>T) pathogenic?

BCL10 p.Pro193Leu (c.578C>T) is classified Uncertain significance in BCL10 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-19). AlphaMissense: ambiguous (0.3454); Very rare (popmax 0.000254%, nfe); Associated with immunodeficiency 37.

What condition is associated with BCL10 p.Pro193Leu (c.578C>T)?

BCL10 p.Pro193Leu (c.578C>T) is associated with immunodeficiency 37 (ClinVar).

How common is BCL10 p.Pro193Leu (c.578C>T) in the general population?

BCL10 p.Pro193Leu (c.578C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about BCL10 p.Pro193Leu (c.578C>T)?

AlphaMissense predicts ambiguous (score 0.3454) — an in-silico prediction, not a clinical call.

BCL10 p.Pro193Leu

c.578C>T · rs943467000 · VCV1507303

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3454 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

immunodeficiency 37

Computational evidence

Protein change
AlphaMissense	0.3454	ambiguous
REVEL	0.427	indeterminate
SaProt	LLR -6.74	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 349 bp · p 0.37 · regional, not allelic
Overall
CADD	27.7	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 0.000254% European (non-Finnish) · 3/1,180,046 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,080 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: BCL10
Protein: p.Pro193Leu
Coding: c.578C>T
MANE Select: NM_003921
dbSNP: rs943467000
Type: single nucleotide variant
Location: chr1:85267751 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI 0.73 (gnomAD)
Structure: AlphaFold pLDDT 70.43 · 5 PDB
Residue 193: 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 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-pro193leu (accessed [today's date]).

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