Is CD40 p.Phe202= (c.606C>T) pathogenic?

CD40 p.Phe202= (c.606C>T) is classified Benign in CD40 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 14.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hyper-IgM syndrome type 3.

What condition is associated with CD40 p.Phe202= (c.606C>T)?

CD40 p.Phe202= (c.606C>T) is associated with hyper-IgM syndrome type 3 (ClinVar).

CD40 p.Phe202=

Q: How common is CD40 p.Phe202= (c.606C>T) in the general population?

CD40 p.Phe202= (c.606C>T) is common (popmax 14.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.606C>T · rs7273698 · VCV338574

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 14.1%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

hyper-IgM syndrome type 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.234	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.1	GERP -3.8, phastCons 0.001
Overall
CADD	5.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.1% African / African-American · 10,514/74,400 alleles

Filtering AF 13.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.8%

Overall 0.77% 12,406/1,611,624 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	14.1%	7
Middle Eastern	1.16%	86
Remaining individualsnot grpmax-eligible	1.04%	96
Admixed American	0.985%	101
Ashkenazi Jewishnot grpmax-eligible	0.183%	548
South Asian	0.138%	727
European (non-Finnish)	0.034%	2,941
East Asian	0.00224%	44,684
Finnishnot grpmax-eligible	0.00157%	63,634

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.Phe202=
Coding: c.606C>T
MANE Select: NM_001250
dbSNP: rs7273698
Type: single nucleotide variant
Location: chr20:46128184 (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

Disease context

hyper-IgM syndrome type 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD40 c.*178G>A Uncertain significance ★★ same condition
CD40 c.*547A>T Uncertain significance ★★ same condition
CD40 c.403+20A>G Benign/Likely benign ★★ same condition
CD40 c.52-15C>T Benign/Likely benign ★★ same condition
CD40 c.559+36G>C Benign ★★ same condition
CD40 c.-1T>C Benign/Likely benign ★★ same condition
CD40 c.*135C>G Benign ★★ same condition
CD40 c.*316G>C Benign ★★ 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/cd40-p-phe202 (accessed [today's date]).

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