Is CD40 p.Met1fs (c.1del) pathogenic?

CD40 p.Met1fs (c.1del) is classified Likely pathogenic in CD40 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-22). Very rare (popmax 0.00133%, afr).

How common is CD40 p.Met1fs (c.1del) in the general population?

CD40 p.Met1fs (c.1del) is very rare (popmax 0.00133%, afr) (gnomAD).

CD40 p.Met1fs

c.1del · rs1047077710 · VCV2183112

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

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 carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.44	GERP -3.5, phastCons 1
Overall
CADD	21.3	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 · 1/74,928 alleles

Overall 0.00131% 2/152,132 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,928
European (non-Finnish)	8.48e-05%	1,179,473

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.Met1fs
Coding: c.1del
MANE Select: NM_001250
dbSNP: rs1047077710
Type: Deletion
Location: chr20:46118344 (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 p.Ter278AlaextTer? Likely pathogenic ★★ same type
CD40 p.Lys29fs Pathogenic ★ same type
CD40 p.Thr96fs Pathogenic ★ same type
CD40 c.257-17_257-14del Likely benign ★ same type
CD40 c.498-30_498-11del Likely benign ★ same type
CD40 c.646+17_646+18del Likely benign ★ same type
CD40 c.647-14_647-3del Likely benign ★ same type
CD40 c.647-16_647-3del Likely benign ★ 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-met1fs (accessed [today's date]).

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