Is BCL10 p.Lys115Gln (c.343A>C) pathogenic?

BCL10 p.Lys115Gln (c.343A>C) is classified Uncertain significance in BCL10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). AlphaMissense: likely benign (0.1441); Very rare (popmax 0.000171%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BCL10 p.Lys115Gln (c.343A>C)?

BCL10 p.Lys115Gln (c.343A>C) is associated with Inborn genetic diseases (ClinVar).

How common is BCL10 p.Lys115Gln (c.343A>C) in the general population?

BCL10 p.Lys115Gln (c.343A>C) is very rare (popmax 0.000171%, nfe) (gnomAD).

What do computational predictors say about BCL10 p.Lys115Gln (c.343A>C)?

AlphaMissense predicts likely benign (score 0.1441) — an in-silico prediction, not a clinical call.

BCL10 p.Lys115Gln

c.343A>C · rs2527103047 · VCV3133376

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1441 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1441	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -6.56	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 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	23.0	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 0.000171% European (non-Finnish) · 2/1,171,198 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000139% 2/1,441,422 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.Lys115Gln
Coding: c.343A>C
MANE Select: NM_003921
dbSNP: rs2527103047
Type: single nucleotide variant
Location: chr1:85270621 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI 0.73 (gnomAD)
Structure: AlphaFold pLDDT 70.43 · 5 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BCL10 p.Cys119Tyr Uncertain significance ★★ ⚠ same condition
BCL10 p.Ile96Val Uncertain significance ★★ ⚠ same condition
BCL10 p.Leu177Ile Uncertain significance ★★ ⚠ same condition
BCL10 p.Glu10Ala Uncertain significance ★ ⚠ same condition
BCL10 p.Pro6Gln Uncertain significance ★ ⚠ same condition
BCL10 p.Thr214Ala Uncertain significance ★ ⚠ same condition
BCL10 p.Thr52Ile Uncertain significance ★ ⚠ same condition
BCL10 p.Arg232Ter Uncertain significance ★★ 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/bcl10-p-lys115gln (accessed [today's date]).

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