Is CD40 p.Glu53Ter (c.157G>T) pathogenic?

CD40 p.Glu53Ter (c.157G>T) is classified Pathogenic in CD40 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-21). Very rare (popmax 0.00133%, afr).

How common is CD40 p.Glu53Ter (c.157G>T) in the general population?

CD40 p.Glu53Ter (c.157G>T) is very rare (popmax 0.00133%, afr) (gnomAD).

CD40 p.Glu53Ter

c.157G>T · rs2515708304 · VCV2024847

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 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 9
Splicing
SpliceAI	Δ0.25	acceptor loss · deltas
Pangolin	Δ0.32	loss · gain 0.10 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.3	GERP 0.48, phastCons 0.038
Overall
CADD	34.0	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 0.00133% African / African-American · 1/75,040 alleles

Overall 6.84e-05% 1/1,461,886 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: CD40
Protein: p.Glu53Ter
Coding: c.157G>T
MANE Select: NM_001250
dbSNP: rs2515708304
Type: single nucleotide variant
Location: chr20:46122259 (GRCh38)
Gene constraint: LOEUF 0.677 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 81.10 · 14 PDB
Residue 53: a disulfide bond; a β-strand

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-glu53ter (accessed [today's date]).

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