Is CD40 p.Trp11Ter (c.33G>A) pathogenic?

CD40 p.Trp11Ter (c.33G>A) is classified Pathogenic in CD40 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-21). Very rare (popmax 8.47e-05%, nfe).

How common is CD40 p.Trp11Ter (c.33G>A) in the general population?

CD40 p.Trp11Ter (c.33G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

CD40 p.Trp11Ter

c.33G>A · rs1211645093 · VCV2032027

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 9
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,010 alleles

Overall 6.2e-05% 1/1,614,016 alleles · very rare exomes 0/1,461,782 · genomes 1/152,234 · joint denominator

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: CD40
Protein: p.Trp11Ter
Coding: c.33G>A
MANE Select: NM_001250
dbSNP: rs1211645093
Type: single nucleotide variant
Location: chr20:46118376 (GRCh38)
Gene constraint: LOEUF 0.677 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 81.10 · 14 PDB

Full CD40 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD40 c.256+5G>A Uncertain significance ★★ same type
CD40 c.*178G>A Uncertain significance ★★ same type
CD40 c.*547A>T Uncertain significance ★★ same type
CD40 p.Ala25Ser Uncertain significance ★★ ⚠ same type
CD40 p.Arg123His Uncertain significance ★★ ⚠ same type
CD40 p.Asn180Lys Uncertain significance ★★ ⚠ same type
CD40 p.Glu159Lys Uncertain significance ★★ ⚠ same type
CD40 p.Ile204Val 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/cd40-p-trp11ter (accessed [today's date]).

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