Is CD40 p.Ser155= (c.465A>G) pathogenic?

CD40 p.Ser155= (c.465A>G) is classified Likely benign in CD40 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-16). Ultra-rare (popmax 0.0439%, sas).

How common is CD40 p.Ser155= (c.465A>G) in the general population?

CD40 p.Ser155= (c.465A>G) is ultra-rare (popmax 0.0439%, sas) (gnomAD).

CD40 p.Ser155=

c.465A>G · rs573253733 · VCV2977935

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0439%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.006	GERP -3.9, phastCons 0.033
Overall
CADD	3.482	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0439% South Asian · 40/91,092 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00291% 47/1,614,186 alleles · ultra-rare exomes 40/1,461,860 · genomes 7/152,326 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0439%	2,277
Remaining individualsnot grpmax-eligible	0.0064%	15,627
East Asian	0.00223%	44,866
African / African-American	0.00133%	75,048
European (non-Finnish)	8.47e-05%	1,180,018

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.Ser155=
Coding: c.465A>G
MANE Select: NM_001250
dbSNP: rs573253733
Type: single nucleotide variant
Location: chr20:46123187 (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-ser155 (accessed [today's date]).

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