Is BCL10 p.Asn142Ser (c.425A>G) pathogenic?

BCL10 p.Asn142Ser (c.425A>G) is classified Uncertain significance in BCL10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-10). AlphaMissense: likely benign (0.062); Very rare (popmax 0.000678%, nfe); Associated with immunodeficiency 37.

What condition is associated with BCL10 p.Asn142Ser (c.425A>G)?

BCL10 p.Asn142Ser (c.425A>G) is associated with immunodeficiency 37 (ClinVar).

How common is BCL10 p.Asn142Ser (c.425A>G) in the general population?

BCL10 p.Asn142Ser (c.425A>G) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about BCL10 p.Asn142Ser (c.425A>G)?

AlphaMissense predicts likely benign (score 0.062) — an in-silico prediction, not a clinical call.

BCL10 p.Asn142Ser

c.425A>G · rs1290999992 · VCV2068200

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.062 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 37

Computational evidence

Protein change
AlphaMissense	0.062	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -5.47	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 0.38	GERP -4.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 349 bp · p 0.37 · regional, not allelic
Overall
CADD	12.83	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 0.000678% European (non-Finnish) · 8/1,179,970 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,874 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.Asn142Ser
Coding: c.425A>G
MANE Select: NM_003921
dbSNP: rs1290999992
Type: single nucleotide variant
Location: chr1:85267904 (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

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

Similar variants

BCL10 p.Asn142His Uncertain significance ★ ⚠ same residue
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

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-asn142ser (accessed [today's date]).

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